THE EFFECTS of BILATERAL and UNILATERAL UPPER-BODY ACUTE RESISTANCE EXERCISE on CARDIOVASCULAR FUNCTION a Dissertation Submitted

THE EFFECTS OF BILATERAL AND UNILATERAL UPPER-BODY ACUTE RESISTANCE EXERCISE ON CARDIOVASCULAR FUNCTION

A dissertation submitted to the Kent State University College of Education, Health and Human Services in partial fulfillment of the requirements for the degree of Doctor of Philosophy

By Erica M. Marshall

May 8, 2020

A dissertation written by

Erica M. Marshall

B.S., John Carroll University, 2012

M.S., The University of Akron, 2014

Ph.D., Kent State University, 2020

Approved by

______Director, Doctoral Dissertation Committee

J. Derek Kingsley

______Member, Doctoral Dissertation Committee

Jacob Barkley

______Member, Doctoral Dissertation Committee

Andrew Lepp

Accepted by

______Director, School of Health Sciences

Ellen Glickman

______Dean, College of Education, Health

James C. Hannon and Human Services

MARSHALL, ERICA M., Ph.D., May 2020 Exercise Physiology

THE EFFECTS OF BILATERAL AND UNILATERAL UPPER-BODY ACUTE RESISTANCE EXERCISE ON CARDIOVASCULAR FUNCTION (pp. 141)

Director of Dissertation: J. Derek Kingsley, Ph.D., FACSM

The purpose of the present study was to determine if unilateral upper-body acute

RE would attenuate alterations in measures of cardiovascular function compared to bilateral upper-body acute RE. Twenty moderately active individuals completed upper- body maximal strength testing followed by two acute RE sessions. Measures of hemodynamics, autonomic modulation, central arterial stiffness, pulse wave reflection, and baroreflex sensitivity were measured at Rest and at 10- and 30-minutes during recovery. Interestingly, there were no significant condition by time interactions for any variable. Still, measures of hemodynamics, autonomic modulation, central arterial stiffness, pulse wave reflection and baroreflex sensitivity were significantly altered from

Rest during recovery from upper-body acute RE. Specifically, the hemodynamic measure heart rate was augmented for at least 30 minutes. These changes were accompanied by alterations in measures of autonomic modulation specific to vagal activity, which were predominantly attenuated for at least 30 minutes. Further, central arterial stiffness was increased and measures of pulse wave reflection in terms of the pulse waveform were also augmented for at least 10 and 30 minutes, respectively. Other pulse wave reflection measures indicative of left ventricular function suggested an increase in myocardial workload and decrease in coronary blood flow for at least 30 minutes. Further, baroreflex sensitivity was reduced for at least 30 minutes.

Collectively, this study suggests that unilateral upper-body acute RE does not seem to be an appropriate upper-body acute RE modality to reduce cardiovascular modulation compared to bilateral RE. Nevertheless, both modalities significantly altered cardiovascular function.

ACKNOWLEDGEMENTS

I would like to thank several individuals, without whom I would not have been able to complete this dissertation, and without whom I would not have made it through my doctoral degree. I am especially indebted to my mentor, Dr. J. Derek Kingsley who has not only been encouraging in my career goals, but has given me profound belief in my work and abilities, relentless and unparalleled support, and unwavering guidance.

You have changed my life. I’m very much looking forward to the day where I can provide one of my students a similar experience. I would also like to thank my very good friend, peer and teammate, Dr. Jason C. Parks. This experience wouldn’t have been the same without you. This is just the beginning of our journey.

Secondly, I would like to acknowledge the assistance, advice and time dedicated from my dissertation committee and also the faculty and staff within the Exercise

Science/Physiology program for their support, knowledge, and guidance. Lastly, I would like to thank my family, especially my Mom and Dad. Thank you for allowing me time to dedicate to this doctoral program by providing me with a safe place where there is always food to eat and lots of love to share. I would also like to thank my girlfriend

Maria. Thank you for bringing me not only love, but peace and a soft place to fall throughout this process and beyond.

iii

TABLE OF CONTENTS

Item Page

ACKNOWLEDGEMENTS ...... iii

LIST OF TABLES ...... vii

CHAPTER

I. INTRODUCTION ...... 1 Background ...... 1 Study Rationale ...... 6 Delimitations ...... 10 Limitations ...... 10 List of Abbreviated Terms ...... 11

II. REVIEW OF THE LITERATURE ...... 13 Background ...... 13 Hemodynamics ...... 13 Pulse Wave Reflection ...... 17 Aortic Blood Pressure ...... 21 Aortic Stiffness ...... 22 Cardiac Autonomic Control ...... 24 Baroreflex Modulation ...... 30

III. METHODOLOGY ...... 33 Participant Recruitment ...... 33 Study Design ...... 33 Informed Consent and Questionnaires ...... 34 Anthropometrics ...... 35 Maximal Strength Testing ...... 36 iv

Hemodynamics and Pulse Wave Reflection ...... 37 Carotid-Femoral Pulse Wave Velocity ...... 38 Heart Rate Variability and Heart Rate Complexity ...... 39 Baroreflex Sensitivity ...... 41 Bilateral and Unilateral Upper-Body Acute Resistance Exercise ...... 42 Statistical Analyses ...... 43

IV. AUTONOMIC MODULATION FOLLOWING BILATERAL AND UNILATERAL UPPER-BODY ACUTE RESISTANCE EXERCISE...... 46 Introduction ...... 46 Methods...... 50 Results ...... 55 Discussion ...... 60

V. CHANGES IN PULSE WAVE REFLECTION, CENTRAL ARTERIAL STIFFNESS, AND BAROREFLEX SENSITIVITY FOLLOWING BILATERAL AND UNILATERAL UPPER-BODY ACUTE RESISTANCE EXERCISE ...... 67 Introduction ...... 67 Methods...... 70 Results ...... 76 Discussion ...... 84

VI. SUMMARY ...... 92

APPENDICES ...... 97 APPENDIX A. INFORMED CONSENT...... 98 APPENDIX B. PHYSICAL ACTIVITY READINESS QUESTIONNAIRE ...... 102 APPENDIX C. HEALTH HISTORY QUESTIONNAIRE...... 104 APPENDIX D. LIPID RESEARCH CLINICS QUESTIONNAIRE ...... 106 APPENDIX E. ANTHROPOMETRICS ...... 109 APPENDIX F. MAXIMAL STRENGTH TESTING ...... 111 APPENDIX G. DATA COLLECTION...... 113

APPENDIX H. LIKERT AND VISUAL ANALOG SCALE ...... 116

REFERENCES ...... 118

LIST OF TABLES

Table Page

1. Participant characteristics (N = 20)...... 55

2. Measures of autonomic modulation at rest and during recovery from bilateral and unilateral upper-body acute resistance exercise in moderately active individuals (N = 20)

...... 57

3. Measures of hemodynamics at rest and during recovery from bilateral and unilateral upper-body acute resistance exercise in moderately active individuals (N = 20) ...... 59

4. Participant characteristics (N = 19) ...... 77

5. Upper-body acute resistance exercise (RE) condition workload (N = 19) ...... 78

6. Measures of heart rate and blood pressure at rest and during recovery from bilateral and unilateral upper-body acute resistance exercise in moderately active individuals (N =

19)...... 79

7. Measures of pulse wave reflection at rest and during recovery from bilateral and unilateral upper-body acute resistance exercise in moderately active individuals (N = 19).

...... 81

8. Central arterial stiffness at rest and during recovery from bilateral and unilateral upper- body acute resistance exercise in moderately active individuals (N = 19)...... 83

9. Measures of baroreflex sensitivity at rest and during recovery from bilateral and unilateral upper-body acute resistance exercise in moderately active individuals (n = 19).

...... 84 vii 1

CHAPTER I

INTRODUCTION

Background

It has been suggested that resistance exercise (RE) improves muscular fitness, and reduces the occurrence of, and symptoms associated with, chronic diseases (American

College of Sports, 2009; Feigenbaum & Pollock, 1999). However, literature that has examined the effects of RE on the cardiovascular system are less clear. This is likely due to methodological differences in terms of program variables such exercise order, volume, intensity, time-under-tension, and rest period length that likely invoke different physiological responses (American College of Sports, 2009; Kraemer & Ratamess,

2004).

However, despite these dissimilarities, the majority of the literature suggests that acute RE may produce adverse effects on the cardiovascular system (Fahs, Heffernan, &

Fernhall, 2009; Kingsley, Tai, Mayo, Glasgow, & Marshall, 2017; Tai, Gerhart, Mayo, &

Kingsley, 2018). Particularly, acute RE is suggested to increase measures of hemodynamics such as heart rate (HR) (Fahs et al., 2009; Kingsley, Mayo, Tai, &

Fennell, 2016) and blood pressure (BP) components: systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) (Fahs et al., 2009).

Augmentations in resting HR have been suggested to increase the risk of cardiovascular disease and mortality (Julius et al., 2012). Additionally, augmentations in resting BP components can negatively affect the heart and central arteries, such as the

2 aorta (Kannel, Gordon, & Schwartz, 1971). Large increases in BP may increase tensile stress of the aortic wall and result in a transfer of force from pliable elastin fibers to stiff collagenous fibers, in order to buffer these higher pressures (O'Rourke & Nichols, 2005).

Ultimately, this results in a stiffer aorta. Accordingly, studies have demonstrated increases in aortic stiffness following acute RE (Heffernan, Collier, Kelly, Jae, &

Fernhall, 2007; Kingsley et al., 2016). Aortic stiffness has been associated with an increased risk of cardiovascular disease and cardiovascular related morbidity and mortality (Mackenzie, Wilkinson, & Cockcroft, 2002).

Acute RE may also increase measures of pulse wave reflection (Kingsley et al.,

2017; Tai, Marshall, et al., 2018). It has been demonstrated that acute RE may result in an early return of the reflected pulse wave from the periphery, which may augment the pressure waveform of the successive pulse wave during ventricular ejection (Fahs et al.,

2009; Kingsley et al., 2017; Tai, Marshall, et al., 2018). An augmentation in the pressure waveform may increase SBP and widen pulse pressure (PP), the difference between SBP and DBP. Together, this may alter left ventricular function by increasing the workload of the left ventricle, and reducing the filling time of the coronary arteries, which may lead to ischemia (Kingsley et al., 2017; Tai, Gerhart, et al., 2018; Tai, Marshall, et al., 2018) of the cardiac cells.

Furthermore, acute RE may alter autonomic modulation and baroreflex sensitivity. Several studies have demonstrated persistent reductions in vagal modulation following acute RE (Heffernan, Kelly, Collier, & Fernhall, 2006; Kingsley et al., 2016;

Kingsley et al., 2018). The reduction in vagal modulation following acute RE may increase the risk of an arrhythmia and sudden cardiac death (Albert et al., 2000; Smith,

Kukielka, & Billman, 2005). In addition, acute RE has been suggested to decrease sensitivity of the baroreflex, which regulates BP homeostasis (Heffernan, Collier, et al.,

2007; Kingsley et al., 2018; Mayo, Iglesias-Soler, Carballeira-Fernandez, & Fernandez-

Del-Olmo, 2016). Specifically, decreases in baroreflex sensitivity may result in further sympathetic outflow and decreased vagal tone (Kingwell, Berry, Cameron, Jennings, &

Dart, 1997), which may also increase the risk of an arrhythmia (La Rovere et al., 2001).

Modalities that may attenuate these negative cardiovascular responses are crucial.

To date, most of the studies that have evaluated cardiovascular responses to acute RE have utilized full-body routines (Collier et al., 2010; Heffernan, Collier, et al., 2007;

Heffernan, Sosnoff, Jae, Gates, & Fernhall, 2008; Kingsley et al., 2014; Kingsley et al.,

2016; Tai, Gerhart, et al., 2018), with a few exceptions (Augustine, Nunemacher, &

Heffernan, 2018; Fahs et al., 2009; Tai, Marshall, et al., 2018). Some studies have demonstrated that a full-body routine may result in very different response compared to a split routine (De Freitas et al., 2018; Kingsley et al., 2014). Accordingly, these researchers suggest that upper-body acute RE may have an unfavorable effect on cardiovascular measures relative to hemodynamics (Augustine et al., 2018; Kang,

Chaloupka, Mastrangelo, & Angelucci, 1999; Tai, Marshall, et al., 2018), aortic stiffness

(Augustine et al., 2018; Fahs et al., 2009), pulse wave reflection (Fahs et al., 2009; Tai,

Marshall, et al., 2018), and autonomic modulation (Kingsley et al., 2014). No studies

4 have reported the effects of upper-body acute RE on baroreflex sensitivity. On the contrary, lower-body acute RE has demonstrated increases in SBP, but no change in

DBP, or aortic stiffness (Heffernan, Rossow, et al., 2006).

Researchers suggest that upper-body exercise produces greater augmentations in

HR and BP contributing to an increase in total peripheral resistance (TPR) because a smaller muscle mass must produce a greater percentage of its’ maximal force to produce power (Kang et al., 1999; Sawka, Foley, Pimental, Toner, & Pandolf, 1983). These alterations in HR and BP may be mediated by an increased demand of the core stabilizing muscles, an increased isometric component (core, handgrip), as well as differences in skeletal muscle recruitment (Sawka, 1986). Based on these findings, more studies should utilize upper body RE protocols to elucidate its’ specific mechanisms and effects on the cardiovascular system.

In addition to just upper- or lower-body acute RE on the cardiovasculature, the amount of muscle mass utilized, such as performing the acute RE bilaterally or unilaterally, is also an area of interest. Resistance exercise modalities performed bilaterally and unilaterally are suggested to invoke different cardiovascular responses

(Moreira et al., 2017). However, to our knowledge, only one study has investigated bilateral versus unilateral acute RE in the upper-extremities and how their respective cardiovascular responses differ. Moreira et al. (2017) examined the effect of bilateral and unilateral biceps curl acute RE and reported that bilateral biceps curl acute RE produced greater cardiovascular responses in terms of HR and rate pressure product (RPP),

5 compared to unilateral biceps curl acute RE. Augmentations in RPP (i.e. the product of

HR and SBP) reduce myocardial oxygen consumption and increase the likelihood of ischemia and a myocardial infarction (White, 1999). Therefore, future studies should further examine the differences between bilateral and unilateral RE and the mechanisms that me be mediating different physiological responses.

Researchers have suggested that bilateral and unilateral physiological responses may be related to the greater amount of muscle mass during bilateral acute RE, which produces greater cardiac demand, as well as increased mechanical compression of the peripheral arteries (Moreira et al., 2017). Additionally, a reduction in limb blood flow due to these compressive forces during bilateral acute RE may result in greater lactate accumulation in the working limbs, which may further augment sympathetic outflow

(Jensen-Urstad & Ahlborg, 1992). Unilateral acute RE may result in an attenuated mechanical response of the peripheral arteries, lessening cardiac work, but this is currently unknown. Therefore, future studies should examine the differences between bilateral and unilateral upper-body acute RE and whether one of these modalities results in an attenuated sympathetic response, which may reduce the likelihood of a cardiac event such as an arrhythmia.

As previously mentioned, research investigating bilateral versus unilateral upper- body acute RE is limited. However, it is plausible that unilateral upper-body acute RE may invoke lesser cardiovascular responses in terms of hemodynamics, pulse wave reflection, aortic stiffness, autonomic modulation, and baroreflex sensitivity due to the

6 fact that it 1) requires a smaller amount of muscle mass, 2) induces less compression of the peripheral arteries, and 3) may result in a greater rate of lactate clearance.

Additionally, each of these mechanisms may also contribute to a more rapid reactivation of the vagus nerve post-exercise, which has been shown to be protective against exercise- induced arrhythmias (Billman & Hoskins, 1989). However, to date, no studies have investigated whether this response occurs following unilateral upper-body acute RE.

Therefore, this study seeks to investigate whether performing acute RE unilaterally might attenuate cardiovascular risk as measured by hemodynamics, aortic stiffness, pulse wave reflection, autonomic modulation, and baroreflex sensitivity compared to performing them bilaterally. The results of this study may provide the general population, athletes, as well as health and fitness professionals with information that will help to advance RE prescription that may reduce deleterious cardiovascular parameters, while maximizing muscular strength and hypertrophy.

Study Rationale

Literature regarding the effects of acute RE on hemodynamics, aortic stiffness, pulse wave reflection, autonomic modulation, and baroreflex sensitivity are unclear.

Currently, acute RE performed utilizing upper-body exercise alone seems to impose significant, negative alterations within the cardiovascular system in terms of hemodynamics, aortic stiffness, and pulse wave reflection. Research is needed to elucidate specific program variables that may directly influence these cardiovascular measures in a positive manner. Additionally, investigating acute RE modalities that may

7 attenuate these negative responses in the cardiovasculature are crucial. Therefore, the purpose of this study was to investigate one modality that may attenuate cardiovascular risk, the comparison of bilateral versus unilateral upper-body acute RE on cardiovascular function.

Specific Aim 1

To investigate differences in hemodynamics in young, healthy moderately active individuals at rest and following bilateral and unilateral upper-body acute RE at 10 and

30-minutes post-exercise.

Hypothesis 1a. Hemodynamics, specifically HR and brachial BP, will be increased compared to rest following bilateral and unilateral upper-body acute RE at 10 and 30-minutes post-exercise in young, healthy moderately active individuals.

Hypothesis 1b. Heart rate and brachial BPs will be lower following unilateral upper-body acute RE compared to bilateral ARE at 10 and 30 minutes in young, healthy moderately active individuals.

Specific Aim 2

To investigate differences in pulse wave reflection in young, healthy moderately individuals at rest and following bilateral and unilateral upper-body acute RE at 10 and

30-minutes post-exercise.

Hypothesis 2a. Pulse wave reflection, namely the augmentation index (AIx), AIx normalized to 75bpm (AIx@75), augmentation pressure (AP), subendocardial viability ratio (SEVR), and wasted left ventricular energy (ΔEw) will be increased and time of the

8 reflected wave (Tr) will be decreased compared to rest following bilateral and unilateral upper-body acute RE at 10 and 30 minutes in young, healthy moderately active individuals.

Hypothesis 2b. The AIx, AIx@75bpm, AP, SEVR, and ΔEw will be lower and

Tr will be higher, following unilateral upper-body acute RE compared to bilateral upper- body acute RE at 10 and 30 minutes in young, healthy moderately active individuals.

Specific Aim 3

To examine differences in aortic stiffness, as measured by carotid-femoral pulse wave velocity (cf-PWV), in young, healthy moderately active individuals at rest and following bilateral and unilateral upper-body acute RE at 10 and 30-minutes post- exercise.

Hypothesis 3a. Aortic stiffness will be augmented compared to rest and following acute bilateral upper-body acute RE at 10 and 30 minutes and at 10 minutes following unilateral upper-body acute RE in young, healthy moderately active individuals.

Hypothesis 3b. Aortic stiffness will be lower following unilateral upper-body acute RE compared to bilateral upper-body acute RE at 10 and 30 minutes with a concomitant return to resting measures at 30 minutes in young, healthy moderately active individuals.

Specific Aim 3

To assess differences in autonomic modulation (vagal modulation, sympathovagal balance) and baroreflex sensitivity in young, healthy moderately active individuals at rest, and following bilateral and unilateral upper-body acute RE at 10 and 30-minutes post-exercise.

Hypothesis 3a. Vagal modulation will be attenuated compared to rest and following acute bilateral and unilateral upper-body acute RE at 10 and 30 minutes in young, healthy moderately active individuals.

Hypothesis 3b. There will be greater reductions vagal modulation waveforms following bilateral acute RE compared to unilateral upper-body acute RE at 10 and 30 minutes in young, healthy moderately active individuals.

Hypothesis 3c. Sympathovagal balance will be augmented compared to rest and following bilateral and unilateral upper-body acute RE at 10 and 30 minutes in young, healthy moderately active individuals.

Hypothesis 3d. There will be greater augmentations in sympathovagal balance following bilateral acute RE compared to unilateral upper-body acute RE at 10 and 30 minutes in young, healthy moderately active individuals.

Hypothesis 3e. Baroreflex sensitivity will be attenuated compared to rest and following bilateral and unilateral upper-body acute RE at 10 and 30 minutes in young, healthy moderately active individuals.

Hypothesis 3f. There will be greater reductions in baroreflex sensitivity following bilateral upper-body acute RE at 10 and 30 minutes compared to unilateral upper-body acute RE at 10 and 30 minutes in young, healthy moderately active individuals.

Delimitations

1. All participants (men and women) were between the ages of 18-35 years.

2. All participants were from Northeastern Ohio.

3. All participants maintained their current dietary patterns

4. All participants had moderate experience with resistance exercise, defined as

engaging in strenuous exercise three days per week.

Limitations

This study population consisted of healthy, moderately active men and women between the ages of 18-35 years. Therefore, the results of this study are not applicable to other populations.

List of Abbreviated Terms

1. Augmentation Index (AIx)

2. Augmentation Index Normalized at 75 beats per min (AIx@75)

3. Augmentation Pressure (AP)

4. Autonomic Nervous System (ANS)

5. Cardiac Output (Q)

6. Carotid-Femoral Pulse Wave Velocity (cf-PWV)

7. Diastolic Blood Pressure (DBP)

8. Diastolic Pressure Time Index (DPTI)

9. Dumbbell (DB)

10. Electrocardiogram (ECG)

11. Heart Rate Complexity (HRC)

12. Heart Rate Variability (HRV)

13. High Frequency Power (HF)

14. Low Frequency Power (LF)

15. Low-Frequency Power to High-Frequency Power Ratio (LF: HF)

16. Mean Arterial Pressure (MAP)

17. Normal-to-Normal Interval (NN)

18. Post-Exercise Hypotension (PEH)

19. Pulse Pressure (PP)

20. Rate Pressure Product (RPP)

21. Repetition Maximum (RM)

22. Resistance Exercise (RE)

23. Root Mean Square of Successive Difference of R-R Intervals (RMSSD)

24. Sample Entropy (SampEn)

25. Sinoatrial Node (SA node)

26. Standard Deviation of Normal-to-Normal Interval (SDNN)

27. Subendocardial Viability Ratio (SEVR)

28. Systolic Blood Pressure (SBP)

29. Systolic Pressure Time Index (SPTI)

30. Time of the Reflected Wave (Tr)

31. Total Peripheral Resistance (TPR)

32. Total Power (TP)

33. Valsalva Maneuver (VM)

34. Wasted Left Ventricular Energy (ΔEw)

CHAPTER II

REVIEW OF THE LITERATURE

Background

Resistance exercise is generally associated with improvements to the musculoskeletal system such as increased muscle mass, bone mineral density and physical fitness (Westcott, 2012). However, the effects of RE on the cardiovascular system are unclear. Current literature suggests that acute RE may induce a deleterious effect on the cardiovascular system, and may increase markers associated with cardiovascular diseases (Julius et al., 2012), arrhythmias (Task Force of the European

Society of Cardiology and the North American Society of Pacing and Electrophysiology,

1996), and mortality (Kannel et al., 1971). This section addresses quantitative markers of the cardiovascular system relative to the heart and aorta, as well as their respective responses to acute RE.

Hemodynamics

The HR is directly related to work of the left ventricular and myocardial oxygen consumption (i.e. coronary blood flow). As HR increases, myocardial oxygen supply decreases due to a reduction in time spent in diastole (Boudoulas, Rittgers, Lewis, Leier,

& Weissler, 1979). Acute augmentations in HR are an independent predictor of sudden cardiac death post-exercise (Jouven et al., 2005).

Several studies have demonstrated increases in HR following acute RE

(Augustine et al., 2018; Fahs et al., 2009; Heffernan, Jae, Edwards, Kelly, & Fernhall,

2007; Kingsley et al., 2014; Tai, Marshall, et al., 2018). For example, Kingsley et al.

(2014) reported increases in HR 25 minutes post-exercise compared to rest following upper-body (chest press, seated row), lower-body (leg extension, leg curl), and full-body

(all 4 exercises) acute RE for 3 sets at 100% of the 10 repetition maximum (RM) in resistance-trained individuals. (Fahs et al., 2009) reported increases in HR for up to 30 minutes post-exercise compared to rest following bench press and biceps curl acute RE performed for 4 sets of five repetitions at 75% 1RM and 4 sets of ten repetitions at 75%

1RM, respectively, in young, healthy men. Utilizing a similar protocol, Augustine et al.

(2018) also reported increases in HR in young, healthy women for up to 30 minutes post- exercise. Furthermore, one study demonstrated increases in HR for up to 15 minutes post- exercise following bench press acute RE for 4 sets of eight repetitions at 75% 1RM (Tai,

Marshall, et al., 2018). Further, increases in HR have been reported for up to 25 minutes post-exercise following lower-body acute RE on the leg press and leg extensions performed in an alternating manner for 10 sets of 15repetitions at 75% 1RM (Heffernan,

Jae, Edwards, et al., 2007). Collectively, these studies demonstrate that HR is increased significantly from rest following full-body and segmental (upper and lower) acute RE are augmented for at least 15- to 30-minutes post-exercise.

The hemodynamic response to acute RE has been suggested to be directly related to the amount of active muscle mass utilized (Seals, 1993). However, it is suggested that

15 upper-body acute RE performed bilaterally, despite a small muscle mass, results in a greater hemodynamic response (Moreira et al., 2017). These responses may be explained by a greater blood lactate accumulation in the upper-body that may augment HR (Jensen-

Urstad & Ahlborg, 1992). Additionally, during the concentric phase of upper-body RE, mechanical compression of the peripheral arteries in proximity of the heart could augment TPR, prompting an increase in cardiac output (Q) via augmentations in HR

(Moreira et al., 2017). Some researchers have suggested that the hemodynamic responses, in terms of HR and RPP, in the upper-body may differ depending upon whether the acute RE is performed bilaterally or unilaterally (Moreira et al., 2017), but this remains unclear. This highlights the need to further understand if performing bilateral versus unilateral acute RE may alter the hemodynamic responses.

Augmentations in brachial SBP and brachial DBP are associated with an increased risk for cardiovascular disease and mortality (Kannel et al., 1971). Blood pressure is typically assessed in the periphery, via the brachial artery, and includes SBP and DBP, as well as the derived pulsatile and steady components, PP and MAP

(Domanski, Davis, Pfeffer, Kastantin, & Mitchell, 1999; Franklin, Wong, Larson, &

Levy, 1999). The effect of acute RE on brachial BP remains unclear. This may be due to dissimilarities in the literature in terms of exercise modality, intensity, and duration, which invoke different brachial BP responses (Halliwill, Taylor, & Eckberg, 1996).

Regardless, the body of literature that involves brachial BP responses to acute RE suggests that acute RE performed with a larger muscle mass may attenuate post-exercise

16 brachial BP compared to a smaller muscle mass (De Freitas et al., 2018; Polito &

Farinatti, 2009), known as post-exercise hypotension (PEH) (Halliwill et al., 1996).

Polito and Farinatti (2009) demonstrated that bilateral leg extension (larger muscle mass) decreased brachial SBP and brachial MAP post-exercise compared to bilateral biceps curl (smaller muscle mass). De Freitas et al. (2018) also reported a greater reduction in brachial BP, specifically SBP, DBP, and MAP, following full-body

RE compared to upper-body RE. Further, increases in exercise duration relative to the number of exercises (Simao, Fleck, Polito, Monteiro, & Farinatti, 2005), and sets performed, may also result in a PEH (Figueiredo et al., 2015; Polito & Farinatti, 2009).

Figueiredo et al. (2015) reported that brachial SBP, brachial DBP, and brachial MAP were further attenuated following three sets of bench press, lat pull down, shoulder press, biceps curl, triceps extension, leg press, leg extension, and leg curl acute RE compared to a single set. Another study also reported a greater reduction in brachial SBP, brachial

DBP, and brachial MAP following ten sets of bilateral leg extension versus six sets with no change in BP following bilateral biceps curl (Polito & Farinatti, 2009).

While some studies demonstrate PEH following acute RE (Figueiredo et al.,

2015; Polito & Farinatti, 2009), this is not universal (Tai, Marshall, et al., 2018). For example, (Tai, Marshall, et al., 2018) reported that bench press acute RE performed for 4 sets of eight repetitions at 75% 1RM resulted in no change in brachial SBP or brachial

DBP. On the contrary, (Fahs et al., 2009) reported an increase in brachial SBP following bench press and biceps curl performed for 4 sets of five repetitions at 85% 1RM and 4

17 sets of ten repetitions at 75% 1RM. However, these reported differences may be due to increases in amount of active muscle mass recruited. Based on these data, future studies should utilize existing protocols to better understand how various program variables affect brachial BP.

The use of other program variables such as performing the RE bilaterally as opposed to unilaterally, may also result in differing hemodynamic responses. Currently, only study has compared cardiovascular responses in the upper body with bilateral and unilateral acute RE performed on the biceps curl. Moreira et al. (2017) reported a reduction in HR and RPP following unilateral biceps curl. Additional studies are warranted to give information on the differing hemodynamic responses following bilateral and unilateral acute RE and whether these responses differ.

Pulse Wave Reflection

Pulse wave analysis is a technique that allows recording of pulse wave propagation and pulse wave reflection. It is commonly assessed using applanation tonometry, which involves flattening of an artery against underlying bone, or via volumetric displacement of a cuff that is placed around the upper arm to assess the pulse of the brachial artery (Butlin & Qasem, 2017). The pulse wave consists of both a forward and reflected pulse wave. During ventricular ejection, a forward traveling pulse wave begins in the aorta and descends the arterial tree. The branching of the arterial tree in the circulation (bifurcation) produces a second, reflected wave that ascends the aorta and returns back to the heart (O'Rourke, Adji, Namasivayam, & Mok, 2011).

Pulse wave reflection parameters include, but are not limited to, the AIx,

AIx@75, time of the reflected wave (Tr), SEVR, and Ew. The AIx is calculated as the ratio between AP and PP and expressed as a percentage (Butlin & Qasem, 2017). The augmentation of the pulse wave, or AP, is caused by early return of the reflected wave during systole (Nichols, 2005) and is calculated as systolic pressure minus inflection pressure (Butlin & Qasem, 2017). An increase in the AIx is a strong predictor of coronary heart disease and has been linked to hypertension, hypercholesterolemia, diabetes mellitus, and smoking. The AIx@75 is calculated similarly with the exception of applying a fixed HR of 75 beats per min in order to control for the inverse relationship that has been observed between the AIx and HR (Wilkinson et al., 2000). Tr refers to the round-trip travel time of the pulse wave from the aorta to the femoral bifurcation and back (Laurent et al., 2001). It has been suggested that an increase in Tr by 10 milliseconds has been associated with a lower risk of a myocardial infarction, stroke, and cardiac death (Weber et al., 2010). Collectively, these data provide useful information on functioning of the heart and aorta and may be used to better predict cardiovascular events.

The SEVR and Ew parameters indicate coronary blood flow and wasted energy of the left ventricle, respectively. Typically, the heart receives oxygenated blood via the coronary arteries during diastole (Fokkema et al., 2005). However, an early return of the reflected wave during systole can disrupt this process and lead to ischemia in the subendocardium (Buckberg, Fixler, Archie, & Hoffman, 1972). The SEVR is calculated

19 as the ratio of diastolic pressure time index (DPTI) to systolic pressure time index (SPTI).

Specifically, the DPTI refers to the area under the curve during diastole and SPTI denotes the area under the curve during systole. Therefore, a decrease in SEVR indicates a reduction in coronary perfusion. Finally, Ew represents the wasted energy exerted by the left ventricle in order to overcome the BP and the reflected pulse wave from the periphery (Tai, Marshall, et al., 2018). Together, these variables give distinct information regarding left ventricular function, and load placed on the left ventricle.

Acute RE has been demonstrated to increase the AIx and other measures of pulse wave reflection such as Tr and Ew. Researchers have reported increases in the AIx and

AIx@75, SEVR, and Ew, and decreases in Tr, in resistance-trained individuals following full-body, free-weight acute RE consisting of the squat, bench, and deadlift performed for 3 sets of ten repetitions at 75% 1RM (Kingsley et al., 2017; Tai, Gerhart, et al., 2018). Yoon et al. (2010) also reported an increase in the AIx@75 following full- body acute RE performed for 2 sets of 15 repetitions at 60% 1RM for eight exercises in young, healthy individuals. Collectively, these data suggest an increase in measures of pulse wave reflection following full-body acute RE performed at varying intensities.

Other researchers have reported alterations in pulse wave reflections following upper-body acute RE alone. For example, (Tai, Marshall, et al., 2018) reported increases in the AIx, AIx@75, SPTI, and Ew following acute RE performed on the bench press for 4 sets of eight repetitions at 75% 1RM in resistance-trained individuals. (Fahs et al.,

2009) also reported increases in the AIx and AIx@75, as well as decreases in Tr,

20 following 4 sets of five repetitions at 80% 1RM and 4 sets of ten repetitions at 75% 1RM.

In a similar protocol, Augustine et al. (2018) reported increases in the AIx, AIx@75, AP, as well as decreases in time of the reflected wave following 5 sets of five repetitions at the 5RM and 5 sets of ten repetitions at the 10RM. Therefore, these data suggest measures of pulse wave reflection are increased following upper-body acute RE alone.

The mechanisms mediating these acute alterations in measures of pulse wave reflection are unclear. The AIx is dependent upon the intensity and timing of the reflected wave and can be influenced by aortic and peripheral artery stiffness (arterial reservoir pressure) and function of the left ventricle (Heffernan, Jae, Echols, Lepine, &

Fernhall, 2007). Acute RE has been demonstrated to increase time spent in systole (TTI) compared to rest (Heffernan, Jae, Echols, et al., 2007; Kingsley et al., 2017; Tai,

Marshall, et al., 2018). This reduction in diastole post-exercise increases the likelihood of the reflected wave returning during systole, and augmenting the successive aortic waveform, which may explain the alterations in measures of pulse wave reflection, specifically the AIx. Additionally, others have reported a change in mechanical distension of the central or peripheral arterial vessels, such that following acute RE there is a transfer of force from distensible elastic fibers to stiffer collagenous fibers (Fahs et al., 2009). While these mechanisms are not fully understood, data have demonstrated that as MAP increases, there is an increase in recruitment of collagen fibers as elastin fibers are unable to handle large increases in stress of the arterial vessel wall (Armentano et al.,

1991). Further, the magnitude of MAP is proportional to the amount of active muscle

21 mass (Haennel et al., 1992). Collectively, the use of a modality that incorporates a smaller muscle mass, such as unilateral acute RE, may reduce measures of aortic BP and measures of pulse wave reflection due a reduction in MAP. However, no studies have examined the effect of unilateral acute RE on these variables.

Aortic Blood Pressure

Blood Pressure can also be assessed at different portions of the arterial tree, including the central arteries, such as the aorta. It has been suggested that aortic BP may better predict cardiovascular health (McEniery, Cockcroft, Roman, Franklin, &

Wilkinson, 2014). However, there is currently no clinical use or standardization for aortic BP compared to brachial BP, in which standards are well known. Nevertheless, aortic BP may be easily derived by a general transfer function, where aortic BP values are estimated from that of the brachial artery (O'Rourke & Nichols, 2003). Report of both aortic and brachial BP may further illustrate changes in pressure throughout the arterial tree, and provide pertinent information on cardiovascular responses.

Augustine et al. (2018) reported a significant increase in aortic SBP, DBP, and

MAP following upper-body acute RE performed on the bench press and bilateral biceps curl utilizing 5 sets of five repetitions at the 5RM and 10 sets of ten repetitions at the

10RM, respectively, in recreationally active women. However, this finding is not universal. Yoon et al. (2010) reported no change in aortic SBP, DBP, or PP following full-body acute RE performed on the bench press, squat, lat pulldown, biceps curl, leg extension, leg curl, upright row, and triceps extension for 2 sets of 15 repetitions at 60%

1RM. Another study reported no change in aortic BP following upper-body acute RE performed on the bench press for 4 sets of eight repetitions at 75% 1RM (Tai, Marshall, et al., 2018). Collectively, the effect of acute RE on aortic BP remains unclear.

However, this may be due to discrepancies between exercise protocols, and/or timing of the measurements post-exercise. Therefore, future studies should utilize previous protocols of similar intensity, number of repetitions, and exercise selection to further elucidate the effect of acute RE on aortic BP.

Aortic Stiffness

Increases in aortic stiffness may induce deleterious effects on the cardiovascular system and has been associated with an increased risk of cardiovascular disease and cardiovascular related morbidity and mortality (Mackenzie et al., 2002). The aorta is a large conduit vessel composed of primarily elastin and some collagenous components.

Typically, elastin fibers are active during lower BPs, whereas collagenous fibers are active during higher BPs. Collectively, these fibers allow expansion and recoil with each heartbeat and proper BP buffering capabilities (Townsend et al., 2015; Wolinsky &

Glagov, 1964).

Several studies have demonstrated increases in aortic stiffness following acute

RE. For example, full-body acute RE consisting of 3 sets of ten repetitions at 75% 1RM on the squat, bench press, and deadlift has been demonstrated to increase aortic stiffness

(Kingsley et al., 2016; Kingsley et al., 2017). Heffernan, Collier, et al. (2007) and Collier et al. (2010) also reported an increase in aortic stiffness full-body acute RE consisting of

23 bench press, bent over row, leg extension leg curl, shoulder press, biceps curl, close grip bench press, and abdominal crunch for 3 sets of ten repetitions at the 10RM. Conversely,

Heffernan, Jae, Edwards, et al. (2007) reported no change in aortic stiffness following alternating leg press and leg extension acute RE performed for 14 total sets of ten repetitions at 75% 1RM. More importantly, the same study reported an increase in aortic stiffness following repeated Valsalva Maneuver (VM) straining bouts that utilized similar

SBP and DBPs achieved during the lower-body acute RE protocol. Therefore, this study suggests that increases in aortic stiffness may be due to the VM alone, but this remains unclear.

Other researchers have reported similar responses following upper-body acute RE alone. (Fahs et al., 2009) reported an increase in aortic stiffness following 4 sets of five repetitions at 80% 1RM and 4 sets of ten repetitions at 75% 1RM. Another study reported similar increases in aortic stiffness following 5 sets of five repetitions at the

5RM and 5 sets of ten repetitions at the 10RM (Augustine et al., 2018). Taken together, these data demonstrate that upper-body acute RE results in an increase in aortic stiffness.

However, each of these studies utilized bilateral exercise. It is unknown if using unilateral acute RE would attenuate these responses.

Marked increases in stiffness of the aorta following acute RE are likely mediated by a transfer in force from elastin fibers to stiff, collagen fibers, which may be more efficient at handling large increases in BP (Armentano et al., 1991). Further, an increase in collagenous fibers, as well as a decrease in vasoactive substances, such as nitric oxide,

24 may affect the relationship between BP and blood flow (Townsend et al., 2015). Some also suggest that increases in aortic stiffness may be due to increased sympathetic nerve activity (Swierblewska et al., 2010). Ultimately, this may lead to systolic and diastolic dysfunction and remodeling of the left ventricle (Bailey, 2001), thereby increasing the risk of hypertension (Dobrin & Rovick, 1969).

Currently, no studies have investigated the effect of unilateral acute RE and bilateral acute RE on aortic stiffness and whether these two modalities produce similar outcomes. To date, only one study has investigated the effects of bilateral and unilateral acute RE and its effects on the heart and vasculature. In a study by Moreira et al. (2017), participants performed bilateral, unilateral, and alternating acute RE consisting of the biceps curl, leg extension, and barbell row for 3 sets of ten repetitions at 80% 10RM.

Researchers reported that during the bilateral biceps curl exercise that HR and RPP were augmented compared to the unilateral biceps curl. Thus, it is plausible that unilateral acute RE may reduce the workload of the heart, but this remains unknown.

Cardiac Autonomic Control

At the onset of RE, contracting skeletal muscle activates Type III and IV muscle afferents towards that of central command in the medulla oblongata, evoking several cardiovascular and ventilatory changes (Coote, Hilton, & Perez-Gonzalez, 1971).

Specifically, activation of muscle afferents induces changes in autonomic nervous system

(ANS) activity, which serve to regulate HR and help redistribute Q towards that of skeletal muscle in order to meet metabolic demand. These autonomic changes include

25 immediate vagal withdrawal, followed by an increase in sympathetic activity.

Sympathetic activity mediates the release of epinephrine on the sinoatrial node (SA) of the heart, which increases HR, vasoconstriction, and release of catecholamines epinephrine and norepinephrine from the adrenal medulla into circulation (Buckwalter &

Clifford, 2001). On the other hand, the parasympathetic nervous system reduces HR by releasing acetylcholine on the SA node (Task Force of the European Society of

Cardiology and the North American Society of Pacing and Electrophysiology, 1996).

Heart Rate Variability

Autonomic nervous system activity, specifically vagal modulation, may be assessed using Heart Rate Variability (HRV), which involves linear analysis of successive R waves on the ECG, or the R-R interval. Analysis of HRV can be made in both the time-domain and frequency domains. The time-domain quantifies the amount of variability in measurements between successive heartbeats. The HRV time-domain measure includes the root mean square of successive differences between normal-to- normal heartbeats (RMSSD). This measure is indicative of parasympathetic activity, or vagal modulation (Task Force of the European Society of Cardiology and the North

American Society of Pacing and Electrophysiology, 1996).

The frequency-domain indices demonstrate how power varies as a function of frequency, which changes as a result of autonomic modulation of the heart period (Task

Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996). The HRV frequency domain indicates total power (TP) or

26 global ANS activity (Task Force of the European Society of Cardiology and the North

American Society of Pacing and Electrophysiology, 1996). Components of the HRV frequency domain include VLF (<0.04 Hz), LF (0.04-0.15 Hz) and HF (0.15-0.4 Hz)

(Task Force of the European Society of Cardiology and the North American Society of

Pacing and Electrophysiology, 1996). The LF components are mediated by both arms of the ANS, whereas the HF component is mediate only by that of the vagus

(parasympathetic) (Task Force of the European Society of Cardiology and the North

American Society of Pacing and Electrophysiology, 1996)

At rest, the HF component is dominant, with respect to the LF component

(Mitchell, 2012). However, various stressors (i.e. acute RE) may decrease and increase these components, respectively, and affect the balance (LF/HF ratio) between the two branches of the ANS. Several studies have demonstrated persistent reductions in vagal activity following full body and upper-body acute RE as indicated by reductions in HF power and increases in sympathovagal balance (Heffernan, Kelly, et al., 2006; Kingsley et al., 2016; Kingsley et al., 2018). Heffernan, Kelly, et al. (2006) reported that HF power was attenuated following bench press, bent over row, leg extension, leg curl, shoulder press, biceps curl, close grip bench, and abdominal crunch performed for 3 sets of ten repetitions at the 10RM. Similarly, Kingsley et al. (2016) reported a reduction in

HF power following squat, bench press, and deadlift acute RE performed for 3 sets of ten repetitions at 75% 1RM.

The effect of upper-body acute RE on autonomic modulation is suggested to increase similarly to that of the lower-body. In a study by De Freitas et al. (2018), the effects of lower-body (leg extension, leg curl), upper-body (chest press, seated row), and full-body (all four exercises) acute RE performed for 3 sets at 65% 1RM on autonomic modulation was assessed. Authors reported a significant reduction in HF and RMSSD following all acute RE modalities with no differences between conditions. These reductions in vagal activity following acute RE may increase the risk of lethal arrhythmia and sudden cardiac death (Albert et al., 2000; Smith et al., 2005). Due to this, reactivation of the vagus nerve is crucial and though unclear, some have suggested that reactivation is longer in duration with larger muscle mass and greater intensities utilized during the resistance exercise (Okuno, Pedro, Leicht, de Paula Ramos, & Nakamura,

2014). Therefore, it may be advantageous to investigate RE modalities that utilize a smaller amount of active muscle to reduce alterations in measures of HRV, such as performing the acute RE unilaterally.

Heart Rate Complexity

The ANS can also be assessed using Heart Rate Complexity (HRC), or non-linear methods. This approach has been suggested to provide a more dynamic explanation of changes occurring during the heart period (Kuusela, Jartti, Tahvanainen, & Kaila, 2002).

From a physiological standpoint, a normal heartbeat is irregular and non-predictable. This is due to the fractal-like nature of the His-Purkinje system and also sympathetic and vagal influences, which result in chaotic fluctuations of HR (Goldberger, Bhargava, West, &

Mandell, 1985). The HRC spectrum of these chaotic fluctuations appears noisy with constant frequency oscillations. On the other hand, a predictable HRC spectrum possesses only one or two closely spaced frequency peaks. Together, a reduction in chaotic fluctuations and increases in low-frequency oscillations of the HR are associated with increased risk of sudden cardiac death (Goldberger, Rigney, Mietus, Antman, &

Greenwald, 1988). It has also been suggested that these non-linear measures may be more sensitive to change than linear ones (Richman & Moorman, 2000).

Non-linear statistics of HRC include various measures of entropy such Sample

Entropy (SampEn) and Approximate Entropy (ApEn). The ApEn method examines a series of heart periods over time with more frequency and similar epochs resulting in a reduction in ApEn. The SampEn method is similar, but eliminates self-matches, which is proposed to provide a more consistent measure over the sampling period (Richman &

Moorman, 2000). Similar to HRV, HRC has been suggested to be reduced following acute RE. Kingsley et al. (2016) reported a reduction in SampEn following acute RE consisting of 3 sets of ten repetitions at 75% 1RM on the squat, bench press, and deadlift.

The same author also reported a reduction in SampEn following upper-body (seated row, chest press), lower-body (leg extension, leg curl), and full-body (both upper and lower- body) acute RE in resistance-trained individuals performed for 3 sets of 10 repetitions at the 10RM (Kingsley et al., 2014).

As mentioned previously, reactivation of the vagus nerve is longer in duration with larger muscle mass and greater intensities (Okuno et al., 2014). Therefore, it may be

29 advantageous to investigate RE modalities that utilize a smaller amount of active muscle to reduce alterations in measures of autonomic modulation. The use of an exercise modality such as unilateral acute RE may provide a quicker activation of the vagus nerve post-exercise due a reduction in active muscle mass and reduced exercise intensity.

Authors have reported a reduction in SampEn following alternating leg extension and leg curl acute RE performed for 10 sets of 15 repetitions at 75% 1RM (Heffernan et al.,

2008). However, these were not compared to one another bilaterally.

Currently, no studies have investigated the effect of unilateral acute RE on measures of autonomic modulation or compared them to that of bilateral acute RE in the upper body. Literature suggests that the sympathetic response during exercise is partly mediated by an increase in pH that activates afferent nerves (Victor, Bertocci, Pryor, &

Nunnally, 1988). Authors have previously suggested that upper-body acute RE produces a greater increase in lactate accumulation (Jensen-Urstad & Ahlborg, 1992), which may be due to increased mechanical compression of the peripheral arteries during the concentric phase, which reduces skeletal muscle tissue perfusion (Moreira et al.,

2017). Collectively, this may result in a more rapid vagal withdrawal (Tulppo,

Makikallio, Takala, Seppanen, & Huikuri, 1996) concomitant with an increase in sympathetic adrenergic vasoconstrictor tone (Pratley et al., 1994). Wirtz, Wahl,

Kleinoder, and Mester (2014) reported that lactate concentration was greater following arm curl exercise with two arms compared to one arm, which may be due to either differing rates of lactate clearance or a reduction in lactate production. Currently, no

30 studies have examined the effect of unilateral acute RE on the upper-body and its’ effects on autonomic modulation. However, the use of a smaller muscle mass through unilateral acute RE may reduce the pressor reflex, and activate fewer Type III and IV muscle afferents, resulting in reduced sympathetic outflow and a consequent rapid activation of the vagus nerve.

Baroreflex Modulation

The baroreceptors located within the sinuses of the carotid artery and aortic arch are triggered by changes in transmural pressure activated by stretch. The baroreflex serves to maintain homeostasis within the cardiovascular system in terms of BP (Parati et al., 1988). The activation of these receptors transmits a signal to the medulla oblongata and results in reductions in HR, which mediates changes in cardiac output (Q) and BP

(Raven, Fadel, & Smith, 2002).

Baroreflex modulation can be assessed using baroreflex sensitivity, or changes in the R-R interval in responses to changes in systolic BP (Parati & Bilo, 2012). The magnitude of the change in this response induced by a change in transmural pressure in the carotid artery or aortic arch is referred to as baroreflex sensitivity (Parati, Di Rienzo,

& Mancia, 2000). Baroreflex sensitivity is modulated by two factors: 1) the relationship between carotid artery and aortic arch transmural pressure relative to its’ diameter and 2) changes in carotid artery and aortic arch diameter concomitant with alterations in activity of the heart and vasculature mediated by central command (Parati & Bilo, 2012).

The relationship between carotid artery and aortic arch diameter and transmural pressure is mediated by mechanical factors (Parati & Bilo, 2012). The carotid artery and aortic arch expand as transmural pressure increases. The increases in vessel diameter of these arteries activate the stretch-sensitive receptors located within their respective sinuses (Parati & Bilo, 2012). These stretch-sensitive receptors in turn send an afferent signal to central command (medulla oblongata) and result in 1) activation of the vagus nerve 2) release of acetylcholine on the SA node instigating a reduction in HR and Q

(Buckwalter & Clifford, 2001).

Alterations in the baroreceptor-HR reflex may be due to reductions in vessel compliance, or increases in aortic stiffness (Michas et al., 2012). Acute RE has been suggested to decrease sensitivity of the baroreflex. Specifically, aortic stiffness may reduce firing of the baroreceptors, resulting in further sympathetic outflow and decreased vagal tone (Kingwell et al., 1997), which may increase the risk of arrhythmia (La Rovere et al., 2001). Additionally, the baroreflex is strongly mediated by peripheral vasoconstriction (Collins, Augustyniak, Ansorge, & O'Leary, 2001).

Researchers have reported a reduction in baroreflex sensitivity following acute

RE on the squat, bench press, and deadlift at 75% 1RM in resistance-trained men and women (Kingsley et al., 2016; Kingsley et al., 2018). Others have reported similar findings following full-body acute RE (Heffernan, Collier, et al., 2007). Therefore, it is clear from these data that acute RE alters baroreflex sensitivity.

Alterations in baroreceptor sensitivity between the lower and upper body following acute RE are not documented in the literature. Further, no studies have compared exercises modalities such as bilateral and unilateral acute RE and their effect on the baroreflex. It is possible that unilateral upper-body acute RE may attenuate the reduction in baroreceptor sensitivity mediated by a decrease in aortic stiffness, but this remains unknown.

CHAPTER III

METHODOLOGY

Participant Recruitment

The study recruited 20 healthy, moderately active individuals between the ages of

18 and 35 years (Figure 1). Physical activity status was determined using the Lipid

Research Clinic questionnaire (Ainsworth, Jacobs, & Leon, 1993). Individuals were recruited by class presentation, email, as well as posted flyers. Exclusion criteria included the use of medications or supplements known to affect HR or BP, recent smoking history (< 6 months), obesity (defined as a BMI ≥ 30 kg/m2), hypertension

(resting brachial SBP ≥ 130 mmHg or DBP ≥ 80 mmHg), orthopedic problems, open wounds, cancer, known metabolic disease, cardiovascular disease, or renal disease.

Additionally, participants were excluded if their 5 RM or 10 RM exceeded 100 pounds

(each limb) on the DB bench press or DB biceps curl exercise. These criteria were assessed via the Physical Activity Readiness Questionnaire (PARQ), Health History

Questionnaire, and maximal strength testing.

Study Design

All participants first underwent an orientation by the key personnel. During the orientation, participants were explained the protocol and procedures and then completed and signed the informed consent followed by the PARQ, and Health History

Questionnaire, and Lipids Research Clinic Questionnaire to determine study eligibility.

Following consent, determination, and eligibility, participants were assessed for height, weight, and body composition. The first and second visits consisted of maximal strength testing on the DB bench press and DB biceps curl for a 5 RM and 10 RM, respectively.

Maximal strength testing days were executed bilaterally and unilaterally (left and right arm) in a counterbalanced format. The third and fourth visits consisted of bilateral and unilateral upper-body acute RE completed in a counterbalanced format. All visits were carried out approximately 72 hours apart. Measures of cardiovascular function were assessed at rest, 10- and 30-minutes post-exercise (Figure 2). Exercise visits occurred between the hours of seven a.m. to noon in order to control for diurnal variation.

Participants were asked to abstain from caffeine, alcohol, and strenuous exercise for at least 24 hours prior to testing and food for at least three hours. Water could be consumed ad libitum. All women were tested during the early follicular phase of the menstrual cycle (day one through seven) denoted by the start of their menses.

Informed Consent and Questionnaires

During the orientation, participants were asked to sign an informed consent explaining the purpose of the study, procedures, and associated risks. Participants also filled out a PARQ, which consisted of a series of yes or no questions to determine if he or she could safely participate in the study. If a participant answered yes to any of the questions, he or she were excluded from the study. The Health History Questionnaire consisted of nine yes or no questions pertaining to health history (e.g.: pregnancy, diabetes, blood pressure, etc.), as well as questions regarding current use of medications

35 or supplements. If a participant answered yes to any of the questions or indicated use of medication(s) or supplement(s) that may have affected the results of the study and/or his or her safety, he or she was excluded. Finally, participants filled out the Lipid Research

Clinics Questionnaire, which consisted of four questions and used a four-point scoring method to determine physical activity status (Ainsworth et al., 1993). Participants were to be classified as moderately active in order to participate. Individuals who were more, or less active were excluded from the study.

Anthropometrics

Participants’ height and weight were assessed using a stadiometer and balance beam scale (Detecto 448; Cardinal Scale Manufacturing, Web City, MO, USA), respectively. Height was measured to the nearest tenth of a centimeter and weight to the nearest tenth of a pound and then converted to kilograms. Body mass index was calculated as kg/m2. Body composition was measured by seven site skinfold measurement (Lange;

Beta Technology, Santa Cruz, CA, USA). Generalized skinfold equations were used to determine body density from the seven sites appropriately for men (Jackson & Pollock,

1978) and women (Jackson, Pollock, & Ward, 1980).

Body density = 1.112 - (0.00043499 x Sum of Skinfolds) (1)

+ (0.00000055 x Square of the Sum of Skinfold Sites) – (0.00028826 x Age)

Body density = 1.097 - (0.00046971 x sum of skinfolds) (2)

+ (0.00000056 x Square of the Sum of Skinfold Sites) – (0.00012828 x Age)

The Brozek equation was used to calculate percent body fat (Brozek, Grande, Anderson,

& Keys, 1963).

Percent Body Fat = (495 / body density) – 450 (3)

Maximal Strength Testing

Prior to performing maximal strength testing, participants completed a five- minute warm-up on the cycle ergometer (Schwinn Air Dyne; Boulder, Colorado).

Participants were then be given a warm-up of 10 repetitions at a submaximal load on the

DB bench press. A second warm-up was then completed (three to five repetitions) using a submaximal load. During the DB bench press, participants lowered the DBs to chest level, then drove the weight off the chest until reaching full elbow extension. Weight was increased incrementally until the participants could no longer complete the five repetitions. Participants were given five attempts to obtain the heaviest weight for five repetitions. After completing maximal strength testing on the DB bench press, participants warmed up for the DB biceps curl following the same procedure noted above. Participants began with full elbow extension and grasped the DBs with a neutral grip, then supinated the wrists during the concentric phase of the lift until the forearm contacted the biceps. The participant then lowered the weight in a controlled manner until reaching full elbow extension and returned the grip to the neutral position. Weight

37 was then increased until the participant could no longer complete the 10 repetitions through a full range of motion. Participants were allotted two minutes of rest between attempts and exercises to ensure maximal effort on each attempt. The same procedure was utilized for both the bilateral and unilateral upper-body acute RE. During the unilateral upper-body acute RE testing, participants completed maximal testing in both the left and right arm. Limb order was randomized. Cadence was set at a two-one-two duty cycle (two-second concentric, one-second pause, and two-second eccentric).

Hemodynamics and Pulse Wave Reflection

Participants rested quietly for 10 minutes in the supine position in a dimly lit, temperature-controlled (19-22C) laboratory. Following rest, brachial BP was assessed in the supine position using an automated oscillometric cuff in the right arm (AtCor

Medical, SphygmoCor EXCEL Technology, Sydney, Australia). Brachial measurements were made in duplicate until two values were within five mmHg of each other for both brachial SBP and brachial DBP. Approximately one minute was allotted between assessments. The two values within five mmHg of each other were then be averaged and used for subsequent analysis.

The brachial pulse wave was used to generates measures of pulse wave reflection using a valid transfer function (Pauca, O'Rourke, & Kon, 2001). The pressure waveform derived from the SphygmoCor device was used to estimate the augmentation of the aortic pressure wave form. Augmentation of the aortic pressure wave is caused by reflection of the peripheral wave, which is generated by ventricular ejection (O’Rourke & Pauca,

2004). Measures of pulse wave reflection included the AIx, AIx@75, Tr, SEVR, and

ΔEw. The AIx was calculated through the division of the AP and PP and expressed as a percentage (Butlin & Qasem, 2017; O’Rourke & Pauca, 2004). The AIx@75 was calculated in a similar manner where HR was calculated at 75 beats per minute in order to control for the inverse relationship between the AIx and HR (Wilkinson et al., 2000).

Time of the reflected wave was calculated as the transit time from ventricular ejection to the arrival of the reflected wave (Butlin & Qasem, 2017). The SEVR was calculated as the ratio between DPTI, the time spent in diastole and SPTI, the time spent in systole.

Lastly, Ew was calculated as follows to determine the wasted energy exerted by the left ventricle, where 1.333 is the conversion factor for mmHg/s to dyne-seconds/cm2 (Casey,

Curry, Joyner, Charkoudian, & Hart, 2011):

Ew = [(π / 4) × (Augmented Pressure × ΔTr) × 1.333 (4)

Carotid-Femoral Pulse Wave Velocity

Aortic stiffness was assessed via cf-PWV (Townsend et al., 2015) utilizing applanation tonometry (AtCor Medical, SphygmoCor EXCEL Technology, Sydney,

Australia). Carotid-femoral pulse wave velocity was calculated by measuring the difference of the foot-to-foot transit time of the pulse wave from the right common carotid artery and cuff-acquired femoral pulse and dividing it by the estimated length of the aortic path. A single, high fidelity transducer was placed on right common carotid artery in addition to an automated cuff on the most proximal portion of the right leg to

39 measure pressure waveforms over a 10-second epoch. The waveforms were measured between the right common carotid artery and right femoral artery. The distances of the waveforms, which reflect the aortic path, were obtained via straight line tape measurement from the right common carotid artery to the suprasternal notch (proximal), suprasternal notch to top of thigh cuff, and suprasternal notch to right femoral artery

(distal). Distance of the aortic path was then estimated using the subtraction method

((suprasternal notch to the top of the thigh cuff) – (carotid artery to suprasternal notch) –

(femoral artery to top of the thigh cuff)) (Butlin & Qasem, 2017). Each measurement was made in duplicate until the values were within one-tenth m/s. The values were then averaged and recorded. Carotid-femoral pulse wave velocity was assessed at rest, 10- and 30-minutes post-exercise following both bilateral and unilateral upper-body acute RE visits.

Heart Rate Variability and Heart Rate Complexity

All signals were collected using PowerLab data acquisition and LabChart software (AD instruments, Colorado Springs, CO (USA). Participants were prepped with a three lead ECG. Beat-to-beat BP signals were collected using photoplethysmography

(Human Non-Invasive BP (NIBP) Nano; AD Instruments, Colorado Springs, CO). Heart rate and BP measurements were sampled at 1000 and 200 Hertz (Hz), respectively. After collection, the ECG was inspected for ectopic beats, noise, and artifacts. Ectopic beats were manually replaced with interpolated adjacent R wave values (Buchheit, Laursen, &

Ahmaidi, 2007). Heart rate and BP signals were imported into WinCPRS for analysis

(Absolute Aliens, Turku, Finland). A Fast Fourier transformation was used to generate frequency domain measures (i.e.: spectral power).

Heart rate variability was assessed using linear methods in both the frequency and time domains utilizing the normal-to-normal intervals on the QRS complex obtained from the ECG. Specifically, these normal-to-normal intervals were adjacent R-waves following removal of artifact (Task Force of the European Society of Cardiology and the

North American Society of Pacing and Electrophysiology, 1996). The frequency domain illustrated the rate at which the heart beat changed over the heart period (Task Force of the European Society of Cardiology and the North American Society of Pacing and

Electrophysiology, 1996). Frequency domain measures included: TP ( 0.4 Hz), the variance of normal-to-normal RR intervals (Task Force of the European Society of

Cardiology and the North American Society of Pacing and Electrophysiology, 1996); HF power (HF; 0.15- 0.4 Hz), a measure of vagal modulation (Task Force of the European

Society of Cardiology and the North American Society of Pacing and Electrophysiology,

1996); and LF/HF, a measure of sympathovagal balance (Pagani et al., 1984), where the frequency range of LF power is 0.04 to 0.15 Hz (Task Force of the European Society of

Cardiology and the North American Society of Pacing and Electrophysiology, 1996).

The time domain measures denoted how the heartbeat changed over the heart period (Task Force of the European Society of Cardiology and the North American

Society of Pacing and Electrophysiology, 1996). The time domain measure included the square root of the mean squared differences of successive normal-to-normal interval

(RMSSD), which is defined as the square root of the mean squared differences of successive normal-to-normal intervals. The RMSSD was indicative of vagal modulation

(Task Force of the European Society of Cardiology and the North American Society of

Pacing and Electrophysiology, 1996).

Heart rate complexity was assessed using non-linear methods, which provided a dynamic representation of changes occurring during the heart period (Kuusela et al.,

2002). Heart rate complexity was reported as SampEn. Sample entropy was calculated as the probability that two normal-to-normal intervals that are similar over the heart period, remain similar. The SampEn eliminates self-matches, which provides a more consistent interpretation of changes that occurred during the heart period, while reducing self-bias (Richman & Moorman, 2000). The SampEn measure has a range of zero to two, where a value that is closer to zero is indicative of a less chaotic, more predictable heartbeat. On the contrary, a value of closer to two is indicative of chaotic fluctuations of the heartbeat (Richman & Moorman, 2000). All autonomic modulation data was collected with a metronome set at 12 breaths per minute.

Baroreflex Sensitivity

Baroreflex modulation was measured as baroreflex sensitivity and determined using the sequence method of the normal-to-normal interval and SBP. The sequence method requires that three or more consecutive beats are characterized by either increases or decreases in brachial SBP and the normal-to-normal interval of the following beat having changed in the same direction. A threshold was implicated and set at greater than

42 or equal to six milliseconds for the normal-to-normal interval and greater than or equal to one mmHg for brachial SBP (Parati et al., 1988).

Bilateral and Unilateral Upper-Body Acute Resistance Exercise

Participants completed an upper-body acute RE protocol adapted from that of

(Fahs et al., 2009), which has been demonstrated to result in significant alterations to the cardiovascular system in terms of measures of pulse wave reflection and aortic stiffness.

The bilateral and unilateral upper-body acute RE visits were completed in a counterbalanced format. First, participants completed a warm-up on the cycle ergometer

(Schwinn Air Dyne; Boulder, Colorado) for approximately five minutes, followed by a brief warm-up on the DB bench press with 50% of their five RM for 10 repetitions. This was followed by four sets of five repetitions at the five RM. Participants were then given a submaximal warm-up with 50% of their 10 RM for the DB biceps curl, followed by four sets of 10 repetitions at the 10 RM. Participants were given two minutes of rest between sets and exercises during the bilateral and unilateral upper-body acute RE.

During unilateral upper-body acute RE, participants performed the repetitions in either the right or left limb first (randomized), then were given approximately two minutes of rest prior to performing the next set of repetitions in the same limb. This ensured that the unilateral upper-body acute RE matched that of the bilateral upper-body acute RE conditions. Cadence was set at two-one-two duty cycle for all repetitions. If participants could not complete the allotted repetitions, a drop set was initiated whereby weight will was reduced by 5 lbs. per limb until the participant could not complete the 5 or 10

43 repetitions with proper form and cadence. This procedure has been utilized in a previous, similar study (Augustine et al., 2018).

Following Visit 3 and 4, participants were assessed for pain following the bilateral and unilateral upper-body acute RE utilizing the Visual Analogue Scale (VAS)

(Gift, 1989). This scale was comprised of a horizontal line (100mm in length) where participants were asked to draw a perpendicular line indicating their pain intensity ranging from “no pain” to “worst pain possible.” Pain was scored based on prior recommendations: no pain (0–4 mm), mild pain (5–44 mm), moderate pain (45–74 mm), and severe pain (75– 100 mm) (Jensen, Chen, & Brugger, 2003). In addition, likeability of the bilateral and unilateral upper-body acute RE was assessed via the Likert Scale

(Likert, 1932). This scale asked participants to rate the extent to which he or she agreed or disagreed with the following two statements, “I prefer the bilateral upper-body acute resistance exercise” and “I prefer the unilateral upper-body acute resistance exercise.”

Participants were offered a choice of five responses ranging from strongly disagree to strongly agree.

Statistical Analyses

A 2x3 Repeated Measures Analysis of Variance (ANOVA) was used to examine the differences across conditions (bilateral, unilateral) and time (Rest, 10-minutes, 30- minutes post-exercise) on hemodynamics [HR, brachial SBP, brachial DBP, MAP, TPR,

Cardiac Output (Q)], pulse wave reflection [aortic SBP, aortic DBP, AP, AIx, AIx@75,

Tr, SEVR, and Ew], cf-PWV, autonomic modulation [TP, HF, LF/HF, RMSSD,

SampEn], and baroreflex sensitivity. If the ANOVA indicated a significant interaction, paired t-tests were performed a Bonferroni-Holm correction factor. The VAS and Likert scale was assessed utilizing a Mann-Whitney U test in order to determine differences between bilateral and unilateral upper-body acute RE regarding pain and preference. All results were presented as mean  standard deviation. Data analysis was completed using

IBM SPSS Version 21 (Armonk, NY, USA). Sample size was calculated using G*Power version 3.1.9.2 (Faul, Erdfelder, Buchner, & Lang, 2009). The sample size of the present study was based on data collected by Augustine et al. (2018) whereby rest and post- exercise means and standard deviations of cPP were used to calculate an effect size of

0.39. A sample size of 13 participants completing each condition, was estimated to achieve a power of 80%, and an alpha of 0.05. Therefore, twenty participants were recruited in order to achieve power while anticipating the potential of participant dropout.

CHAPTER IV

AUTONOMIC MODULATION FOLLOWING BILATERAL AND UNILATERAL

UPPER-BODY ACUTE RESISTANCE EXERCISE

Introduction

Acute resistance exercise (RE) is known to transiently alter autonomic modulation during the recovery period, mainly by reducing vagal modulation, which collectively serves to alter the cardiac rhythm (Heffernan, Kelly, et al., 2006; Kingsley et al., 2014;

Tai et al., 2019). It is believed that these alterations may increase the risk of an arrhythmia even in healthy individuals, as well as the risk of sudden cardiac death in otherwise healthy individuals with undiagnosed cardiovascular disease (Albert et al.,

2000; Kannankeril, Le, Kadish, & Goldberger, 2004; Smith et al., 2005). It is generally understood that the main mechanism responsible for cardiac recovery is reactivation of the vagus nerve. Further, evidence suggests that a reduction in vagal recovery is associated with a higher risk of cardiac related morality (Smith et al., 2005).

Heart rate variability (HRV) is a widely used non-invasive method to assess autonomic modulation, which involves linear analysis of R-R intervals on the electrocardiogram (ECG) in both the frequency and time domains (Task Force of the

European Society of Cardiology and the North American Society of Pacing and

Electrophysiology, 1996). The variance of R-R intervals, an indication of global autonomic activity is represented as total power (TP) (Task Force of the European

Society of Cardiology and the North American Society of Pacing and Electrophysiology,

1996). The high-frequency (HF) component of the HRV power spectra is suggested to be mediated exclusively by the vagus nerve, whereas the low-frequency (LF) component is mediated by both the vagus nerve and sympathetic nerves (Task Force of the European

Society of Cardiology and the North American Society of Pacing and Electrophysiology,

1996). Further, the ratio of LF power to HF power (LF:HF ratio) is often used to assess overall sympathovagal dominance (Billman & Hoskins, 1989). The time domain measure known as the square root of the mean squared differences of successive R-R intervals (RMSSD), is another HRV measure that is solely indicative of vagus nerve activity (Task Force of the European Society of Cardiology and the North American

Society of Pacing and Electrophysiology, 1996).

However, despite the usefulness of HRV analysis, non-linear methods such as those of heart rate complexity (HRC) may better indicate acute changes occurring over the heart period compared to linear methods (Kuusela et al., 2002; Richman & Moorman,

2000). More specifically, non-linear methods could provide a more accurate representation of changes in the heart period, which are generally considered to be non- homeostatic (i.e. chaotic) (Goldberger, 1991). Sample entropy (SampEn) is one measure of HRC that depicts similarities in the R-R interval over the heart period (Richman &

Moorman, 2000). However, to date these data are limited following acute RE performed in the upper-body (Kingsley et al., 2014).

Current literature suggests that vagal modulation is attenuated following upper- body acute RE as indicated by reductions in TP (Kingsley et al., 2014; Tai et al., 2019),

HF power (De Freitas et al., 2018; Kingsley et al., 2014; Okuno et al., 2014; Tai et al.,

2019), increases in LF:HF ratio (Kingsley et al., 2014), as well as decreases in RMSSD

(De Freitas et al., 2018; Kingsley et al., 2014; Okuno et al., 2014; Tai et al., 2019) and

SampEn (Kingsley et al., 2014). This may be due to the fact that upper-body acute RE compared to lower-body acute RE has been suggested to elicit hemodynamic changes such as an increase in heart rate (HR) (Kang, Chaloupka, Mastrangelo, & Angelucci,

1999; Volianitis, Yoshiga, Nissen, & Secher, 2004) and a decrease in stroke volume (SV)

(Sawka, 1986). Collectively, this serves to increase cardiac output (CO), in addition to an increase in mean arterial pressure (MAP), total peripheral resistance (TPR) (Kang et al.,

1999; Volianitis, Yoshiga, Nissen, & Secher, 2004), and local metabolites (Jensen-Urstad

& Ahlborg, 1992). To date, few studies have explored the effects of performing upper- body acute RE in a bilateral or unilateral manner on the cardiovasculature. However, some researchers have suggested bilateral upper-body acute RE results in a greater increase in compressive forces, which may result in further lactate accumulation in the working limbs, collectively augmenting sympathetic outflow (Jensen-Urstad & Ahlborg,

1992). On the other hand, unilateral upper-body acute RE has been demonstrated to attenuate production of metabolites and/or increase the rate of clearance of these metabolites (Wirtz et al., 2014). Further, Moreira et al. (2017) previously reported that unilateral upper-body acute RE resulted in an attenuated HR and blood pressure (BP)

49 response compared to bilateral upper-body acute RE. Therefore, it is plausible that favorable changes in hemodynamics following unilateral compared to bilateral upper- body acute RE may occur in parallel to increased vagal reactivation during recovery.

To our knowledge, no studies have investigated the effects of bilateral and unilateral upper-body acute RE on measures of autonomic modulation, only those of hemodynamics. Therefore, the purpose of the present study was to compare the effect of bilateral and unilateral upper-body acute RE on measures of autonomic modulation and hemodynamics at rest as well as 10- and 30-minutes during recovery. It was hypothesized that following bilateral upper-body acute RE that: 1) measures of HRV in the frequency domain, namely TP and HF power would be significantly decreased and the LF:HF ratio significantly increased, in addition to significant decreases in the time domain measure, RMSSD, for at least 30 minutes; 2) SampEn would be significantly decreased for at least 30 minutes; 3) and measures of hemodynamics such as HR and CO would be significantly increased and TPR significantly decreased, with no significant changes in SV or MAP for at least 30 minutes. However, the principal hypothesis for this study was that following the unilateral upper-body acute RE, these cardiovascular measures would be recovered by 30 minutes compared to the bilateral upper-body acute

RE.

Methods

Twenty healthy, moderately active, based on their self-reported physical activity status, individuals participated in this study. Physical activity status was determined using the Lipid Research Clinic questionnaire (Ainsworth et al., 1993). Participants were excluded if they had a recent smoking history (< 6 months), obesity (defined as a BMI ≥

30 kg/m2), hypertension (resting systolic blood pressure (SBP) ≥ 130 mmHg or diastolic blood pressure (DBP) ≥ 80 mmHg), orthopedic problems, open wounds, cancer, known metabolic disease, cardiovascular disease, or renal disease, in addition to if they were using medications or supplements known to affect HR or BP. These criteria were assessed during the orientation via the Physical Activity Readiness Questionnaire

(PARQ) and Health History Questionnaire. All participants signed a written informed consent prior to the collection of any anthropometric or autonomic and hemodynamic data. This study was approved by the Institutional Review Board and corresponded to the Declaration of Helsinki.

Following consent and orientation, participants completed four additional visits.

During visit one, participants were first assessed for anthropometrics followed by maximal strength testing on the bilateral dumbbell (DB) bench press and DB biceps curl for a 5-repetition maximum (RM) and 10 RM, respectively. Visit two consisted of maximal strength testing on the unilateral DB bench press and DB biceps curl, which was performed using the same methods as visit one. Finally, visit three and four consisted of bilateral and unilateral upper-body acute RE completed in a counterbalanced format.

During visits three and four, measures of autonomic modulation and hemodynamics were assessed at Rest, and at 10- and 30-minutes during recovery (Figure 2). Both visits were collected at the same time of day ( one hour) and occurred between the hours of six a.m. to noon in order to control for diurnal variation. All visits were at least 72 hours apart.

Participants were asked to abstain from caffeine, alcohol, and strenuous exercise for at least 24 hours and food for at least 3 hours prior to testing. All women were tested during the early follicular phase of the menstrual cycle (day one through seven) denoted by the start of their menses.

Participants’ height and weight were assessed using a stadiometer and balance beam scale (Detecto 448; Cardinal Scale Manufacturing, Web City, MO, USA), respectively. Height was measured to the nearest tenth of a centimeter and weight to the nearest tenth of a pound (lb) and then converted to kilograms to compute BMI.

Participants first completed a five-minute warm-up on the cycle ergometer (Schwinn Air

Dyne; Boulder, Colorado). Following the warm-up, maximal strength testing at the 5RM on the DB bench press and 10RM on the DB biceps curl was carried out utilizing previously described methods (Harman, Carhammer, & Pandorf, 2000). Specifically, participants were given a warm-up at a weight they could easily move for ~10 repetitions.

The weight of the DBs was then increased 5 to 10% and a second warm-up of 3 to 5 repetitions was performed. Thereafter, weight was increased 5 to 10% incrementally until the participant could no longer complete the allotted repetitions or maintain prescribed cadence. Participants were given five attempts to obtain the heaviest weight

52 they could move through a full range of motion for five repetitions with two minutes of rest between attempts and exercises. Further, during visit two, the unilateral upper-body acute RE testing was completed in both the left and right arm. Cadence was set at a two- one-two duty cycle for all repetitions performed (two-second concentric, one-second pause, and two-second eccentric (Fahs et al., 2009). The same spotter was present at all testing sessions to ensure the safety of the participants.

Beat-to-beat heart HR signals were collected using PowerLab data acquisition and

LabChart software (AD instruments, Colorado Springs, CO (USA)). All autonomic modulation data were collected with a metronome set at 12 breaths per minute. The ECG reading was collected at a sampling rate of 1000 Hertz (Hz). After collection, all ECGs were inspected for ectopic beats, noise, and artifact. Any ectopic beats were manually replaced with interpolated adjacent R wave values (Buchheit et al., 2007). Following,

HR signals were imported into WinCPRS (Absolute Aliens, Turku, Finland) for generation and analysis of R-R intervals in the frequency and time domains. Frequency domain measures were generated with a Fast Fourier transformation (Task Force of the

European Society of Cardiology and the North American Society of Pacing and

Electrophysiology, 1996).

Heart rate complexity was assessed using non-linear methods, which provides a dynamic representation of changes occurring during the heart period (Kuusela et al.,

2002). Heart rate complexity was reported as SampEn and was calculated as the probability that two normal-to-normal intervals that are similar over the heart period,

53 remain similar and has a range of zero to two, where a value that is closer to zero is indicative of a less chaotic, more predictable heartbeat (Richman & Moorman, 2000).

Beat-to-beat BP signals were collected using photoplethysmography (Human

Non-Invasive BP (NIBP) Nano; AD Instruments, Colorado Springs, CO (USA)). The pressure waveforms obtained were used to assess HR, SV, CO, MAP, and TPR. The

Modelflow technique utilizes the pressure of the index finger in order to calculate CO

(Bogert & van Lieshout, 2005; Wesseling, Jansen, Settels, & Schreuder, 1993), which has been demonstrated to be a valid and reliable non-invasive estimate (Sugawara et al.,

2003). The SV was derived from HR and CO (Bogert & van Lieshout, 2005). Finally,

TPR was calculated as MAP divided by CO.

Participants completed an upper-body acute RE protocol adapted from that of

Fahs et al. (2009). In that particular study, the authors reported that their acute RE protocol resulted in significant alterations to the cardiovascular system, namely hemodynamics (i.e. HR, MAP, TPR). In the present study, following collection of resting measures, participants completed a warm-up similar to that of visit one and two followed by four sets of five repetitions at their five RM. The same warm-up procedure was given for the DB biceps curl, followed by 4 sets of 10 repetitions at the 10RM.

Participants were given two minutes of rest between sets and exercises. During unilateral upper-body acute RE, participants performed the repetitions in either the right or left limb first, which was randomized, then were given approximately two minutes of rest prior to performing the next set of repetitions in the same limb. This procedure was followed to

54 ensure that time-under-tension during the unilateral upper-body acute RE matched that of the bilateral upper-body acute RE condition. Similar to maximal strength testing, cadence was set at two-one-two duty cycle for all repetitions (Fahs, Heffernan, and

Fernhall (2009b). If participants could not complete the allotted repetitions, a drop set was initiated whereby weight was reduced 2.2 kg per limb until the participant could complete the allotted repetitions with proper form and cadence. The same spotter was present to ensure safety, proper form, and cadence.

Statistical Analyses

All data were first checked for extreme outliers and assumptions of Analysis of

Variance (ANOVA) using IBM SPSS Version 21 (Armonk, NY, USA). Tests of

Normality were conducted via Shapiro-Wilk. Violations of sphericity were adjusted utilizing a Greenhouse-Geisser correction. Independent samples-tests were conducted in order to determine anthropometric differences between men and women participants.

Variables that were not normally distributed (TP, HF power, LF power, LF:HF ratio and

RMSSD) were corrected with a logarithmic (ln) transformation. A 2x3 Repeated

Measures ANOVA was used to examine the differences across conditions (Bilateral,

Unilateral) on the repeated factor of time (Rest, 10- and 30-minutes) on autonomic modulation (ln TP, ln HF power, ln LF, ln LF:HF ratio, ln RMSSD, and SampEn) and

2 hemodynamics (HR, SV, CO, MAP, and TPR). Partial eta squared (p ) was used to assess the effect size of each dependent variable. Significant interactions were analyzed using paired t-tests with a Holm-Bonferroni correction factor (Holm, 1979). All results

55 are presented as mean  standard deviation (SD). Sample size was calculated using

G*Power version 3.1.9.2 (Faul et al., 2009). The sample size of the present study was based on measures of autonomic modulation collected by (Tai et al., 2019) whereby rest and post-exercise means and standard deviations of ln TP power were used to estimate

Cohen’s d. A sample size of 4 participants completing each condition, was estimated to achieve a power of 80% based on an effect size of 0.89 and an alpha of 0.05.

Results

Participant characteristics are presented in Table 1. There were significant (p 

0.001) differences between men in women in terms of height and weight, such that men were heavier and taller than women.

Table 1 Participant characteristics (N = 20).

Characteristic Men (N = 10) Women (N= 10)

Age (yr) 23 ± 3 23 ± 3

Height (m) 1.8 ± 0.1§ 1.7 ± 0.0

Weight (kg) 81.9 ± 10.1§ 67.8 ± 10.7

BMI (kg/m2) 25.9 ± 3.0 24.5 ± 3.0

BMI, body mass index. Data presented are mean ± SD. §Significantly different from women (p  0.001).

Measures of autonomic modulation are presented in Table 2. There were no significant (p > 0.05) condition by time interactions for measures of autonomic

2 modulation. There were significant main effects of time for the ln TP (p  0.001, np =

2 2 0.6), ln HF power (p  0.001, np = 0.6), ln LF (p  0.001, np = 0.5), ln RMSSD (p 

2 2 0.001, np = 0.7), and SampEn (p = 0.011, np = 0.2). The ln TP, ln HF power, and ln

RMSSD were significantly decreased at both 10 minutes and 30 minutes compared to

Rest. These measures were also significantly decreased from 10 minutes to 30 minutes compared to Rest. Further, ln LF was reduced at 10 minutes compared to Rest but increased at 30 minutes compared to 10 minutes such that it was similar to Rest. Lastly, there was a significant reduction in SampEn only at 10 minutes compared to Rest, with

SampEn being fully recovered by 30 minutes. There were no significant (p > 0.05) main effects of time for the ln LF:HF ratio.

Table 2

Measures of autonomic modulation at rest and during recovery from bilateral and unilateral upper-body acute resistance exercise in moderately active individuals (N =

20).

Bilateral Unilateral

Rest 10 minutes 30 minutes Rest 10 minutes 30 minutes

HF (ln ms2) 7.7  1.2 6.5  1.6* 7.4  1.2*† 7.7  1.3 6.5  1.6* 7.1 1.4*†

LF (ln ms2) 6.9  1.0 5.9  1.3* 6.6  1.1† 6.8  1.0 6.1  1.1* 6.6  1.1†

8.3  TP (ln ms2) 8.5  1.0 7.6  1.3* 8.2  1.0*† 8.5  1.0 7.8  1.2* 1.1*†

LF/HF ratio (ln) 3.7  0.7 3.9  0.8 3.8  0.8 3.7  0.9 4.1  0.9 4.2  0.7

4.1  RMSSD (ln ms) 4.4  0.7 3.7  0.9* 4.3 0.7*† 4.3  0.7 3.7  0.9* 0.8*†

SampEn 1.5  0.2 1.4  0.2* 1.5  0.2 1.6  0.2 1.4  0.2* 1.5  0.2

HF, High-Frequency power; LF, Low-Frequency power; MAP, Mean Arterial Pressure, RMSSD, Root

Mean Square of Successive Differences Between Normal-to-Normal Heart Beats; SampEn, Sample

Entropy; TP, Total Power. Data presented are mean ± SD. *Significantly different from Rest (p  0.01),

†Significantly different from 10 minutes (p  0.01).

Measures of hemodynamics are presented in Table 3. There were no significant

(p > 0.05) condition by time interactions for measures of hemodynamics. However, there

2 2 were significant main effects of time for HR (p  0.001, np = 0.7), CO (p = 0.009, np =

2 2 0.23), MAP (p  0.001, np = 0.5) and TPR (p  0.001, np = 0.4). Specifically, HR was increased from Rest at both 10 minutes and 30 minutes, but also decreased from 10 minutes to 30 minutes such that it remained above Rest. MAP was decreased at both 10 minutes to 30 minutes compared to Rest. However, MAP increased from 10 minutes to

30 minutes such that it was greater than Rest. Further, CO and TPR were increased and decreased from Rest to 10 minutes, respectively. TPR was also increased from 10 minutes to 30 minutes, such that it was similar to Rest. There were no significant main effects of time for SV (p > 0.05).

Table 3

Measures of hemodynamics at rest and during recovery from bilateral and unilateral upper-body acute resistance exercise in moderately active individuals (N = 20).

Bilateral Unilateral

Rest 10 minutes 30 minutes Rest 10 minutes 30 minutes

HR (bpm) 54  6 67  10* 60  8*† 56  7 67  11* 62  9*†

SV (ml/kg/min) 88.2  20.2 84.0  15.3 84.4  12 90.3  16.6 83.7  15.7 86.0  15.8

CO (L/min) 4.9  1.3 5.7  1.3* 5.3  1.1 5.1  1.1 5.5  1.6* 5.5  1.4

MAP (mmHg) 77  7 74  6* 80  4*† 80  9 76  7* 83  7*†

TPR (mmHg.min/ L) 1.0  0.2 0.8  0.2* 1.0  0.2† 1.0  0.2 0.9  0.3* 1.0  0.4†

HR, Heart Rate; MAP, Mean Arterial Pressure; SV, Stroke Volume; TPR, Total Peripheral Resistance.

Data presented are mean ± SD. *Significantly different from Rest (p  0.01), †Significantly different from

10 minutes (p  0.01).

Discussion

This study investigated the effects of bilateral and unilateral upper-body acute RE on measures of autonomic modulation and hemodynamics in healthy young, moderately active individuals. The primary findings of the present study are somewhat in disagreement with the hypotheses, such that bilateral and unilateral upper-body acute RE instead produced similar alterations in measures of autonomic modulation and hemodynamics over time. Nevertheless, this study suggests that bilateral and unilateral upper-body acute RE both resulted in significant decreases in HRV measures of vagal modulation as demonstrated by decreases in ln HF power and ln RMSSD for at least 30 minutes, in addition to the HRC measure SampEn for at least 10 minutes during recovery.

Further, these alterations were primarily accompanied by hemodynamic changes such as increases in HR and CO, as well as decreases in MAP and TPR. As previously stated, changes in autonomic modulation may be better described with measures of HRC compared to HRV due to its non-linear measurement, which considers the non- homeostatic nature of the heart period. Given this information, this study suggests that recovery of autonomic modulation following bilateral and unilateral upper-body acute RE is at least 10 minutes, and recovery of hemodynamic measures, particularly HR, is at least 30 minutes.

The observed reduction in HRV measures of autonomic modulation following upper-body acute RE in the present study are consistent with the current literature (De

Freitas et al., 2018; Kingsley et al., 2014; Tai et al., 2019). The present study reported a

61 reduction in ln TP following both bilateral and unilateral upper-body acute RE at 10 and

30 minutes during recovery. Tai et al. (2019) also reported a reduction in ln TP, but only at 25 to 30 minutes during recovery compared to rest. However, Kingsley et al. (2014) reported no change in ln TP at similar time points. Nevertheless, Tai et al. (2019) and

Kingsley et al. (2014) also reported a reduction in ln HF power and ln RMSSD, but a non-significant change in ln LF power following upper-body acute RE consisting of the barbell bench press, or machine row and chest press, respectively. It is possible that changes in ln LF power in the present study may be solely due to reductions in vagal activity, but this is merely speculation. Further, Tai et al. (2019) also reported an increase in the ln LF:HF ratio, which was neither observed by Kingsley et al. (2014) nor the present study. It is possible that reductions in vagal activity in the ln HF power and ln

LF power prompted no change in the LF:HF ratio. De Freitas et al. (2018) also reported a reduction in the RMSSD, but this measure was slightly different compared to the present study limiting direction comparisons since it was not logarithmically transformed.

However, De Freitas et al. (2018) reported a decrease in the RMSSD by ~79% and ~53% at 10 and 30-minutes, respectively. This is similar in direction but greater in magnitude compared to the present study, which was ~16% at 10 minutes and ~6% at 30 minutes.

These dissimilarities may be attributed to differences in the upper-body RE protocol as previously described, or the fact that the study by De Freitas et al. (2018) only included men. However, while a greater RE volume may contribute to these differences

(Figueiredo et al., 2015), whether sex influences measures of autonomic modulation are

62 unclear (Kingsley et al., 2018; Mendonca et al., 2010). Collectively, these studies support that vagal activity is attenuated during recovery from upper-body acute RE, which may be affected by RE volume, but its effect on sympathovagal dominance remains unclear.

Further, changes in measures of HRV were accompanied by changes in the HRC measure SampEn in the present study up to 10 minutes. Specifically, SampEn was reduced only at 10 minutes during recovery whereas HRV measures such as ln HF, ln TP, and ln RMSSD were attenuated for at least 30 minutes. It is unclear why SampEn, which may be considered a more sensitive measure of autonomic modulation was recovered by

30 minutes, whereas less sensitive HRV measures of vagal modulation remained attenuated. It is possible that SampEn may truly be a better indication of recovery of autonomic modulation, or linear measures of HRV may overestimate recovery, but this is conjecture and more data are needed. Further, Kingsley et al. (2014) also reported a reduction in SampEn, but at 25-30 minutes during recovery, which again was not observed in the present study. It is likely that variations in post-hoc tests between the two studies may account for these differences with the present study utilizing a more conservative post-hoc correction factor. However, these different responses may have also been influenced by training status. The individuals in the study by Kingsley et al.

(2014) were resistance-trained individuals, unlike those in the present study who were moderately active. Further, as SampEn may be a more precise measure, it is possible that the exercise protocol in the present study was not enough to provoke significant changes

63 in vagal modulation at 30 minutes during recovery. In the present study, individuals performed 3 sets of the DB bench press and DB biceps curl at the 5 RM and 10 RM, respectively. But, individuals in the study by Kingsley et al. (2014) performed the machine chest press and row for 3 sets at the 10 RM. However, both studies utilized a similar rest period length between sets and exercises (i.e. two minutes). The latter protocol likely involves a larger amount of active muscle mass that could help to explain these differences (Machado-Vidotti et al., 2014; Seals, 1993). Moreover, upper-body acute RE does seem to alter HRC in terms of SampEn. However, recovery of SampEn in particular may be dicated by the amount of active muscle mass utilized, but again this is speculation.

Alterations in measures of autonomic modulation, specifically a reduction in vagal activity, were accompanied by significant changes in hemodynamics in the present study that are similar to the literature (De Freitas et al., 2018; Kingsley et al., 2014; Tai et al., 2019). Specifically, Kingsley et al. (2014) and Tai et al. (2019) also reported an increase in HR up to 30 minutes during recovery. The observed increase in HR is likely due to the reduction in vagal activity. The augmentation in HR in the present study prompted an increase in CO as SV was not significantly altered during recovery.

Furthermore, the present study also observed modest reductions in MAP and TPR. The decrease in MAP during the recovery time points is similar to De Freitas et al. (2018) which also reported a reduction in MAP at 10 minutes during recovery. The acute RE protocol by De Freitas et al. (2018) was quite different from the present study as it

64 consisted of a greater number of exercises and sets performed (i.e. 18 sets of the bench press, T-bar row, and biceps curl at 65% of the 1RM). Though we previously stated that upper-body acute RE prompts increases in MAP and TPR, these responses seem to be recovered by 30 minutes in the present study. Together, these responses may have been mediated by a release in local metabolites that could have promoted an increase in vasodilation in the vasculature thereby reducing MAP and TPR.

Collectively, this study suggests that measures of autonomic modulation and hemodynamics following bilateral and unilateral upper-body acute RE do not differ.

These results are in disagreement with those of Moreira et al. (2017) who suggested that bilateral and unilateral upper-body acute RE produce different cardiovascular responses.

In the study by Moreira et al. (2017), individuals performed bilateral and unilateral biceps curl exercise for 3 sets of 10 repetitions at the 10RM. The time of measurement between that study and the present study may account for differences in findings as measures of hemodynamics were collected by Moreira et al. (2017) immediately after the last repetition of the upper-body acute RE bout. It is likely that these differences in HR may have disappeared by 10 minutes in the present study. Additionally, the exercise protocol by Moreira et al. (2017) utilized a small active muscle mass (biceps) compared to the present study that used a larger active muscle mass (chest and biceps) that might also help to explain these differences. Further, the prescribed rest between sets for unilateral upper-body acute RE by Moreira et al. (2017) was not thoroughly described. In the present study, a rest period of two minutes was given prior to the start of the successive

65 set in the same limb. However, this greatly limited the rest period occurring before the repetitions were performed in the opposite limb. This lack of rest during the unilateral upper-body acute RE may have served to create higher cardiac stress (Lemos et al.,

2018). In addition, the unilateral upper-body acute RE also involved greater core stabilization compared to the bilateral upper-body acute RE and cardiovascular responses are suggested to be muscle mass dependent (Machado-Vidotti et al., 2014; Seals, 1993).

Collectively, these factors during the unilateral upper-body acute RE may have allowed for similar responses to that of the bilateral upper-body acute RE on measures of autonomic modulation and hemodynamics during recovery.

There are a few limitations in the present study. Specifically, this study included both men and women, whom had differences in terms of height and weight, with men being both taller and heavier. However, these characteristics were not run as a covariate due to the failed assumption of linearity between the covariate and measures of autonomic modulation and hemodynamics. Additionally, there are also considerable hormonal differences between men and women, such that women have inherently higher levels of estrogen, which is known to be cardioprotective. However, sex differences could not be determined in this study due to insufficient power. Previous literature has reported no sex differences in resistance-trained individuals (Kingsley et al., 2018), but whether this is also true in moderately active individuals is unknown. Additionally, the

Valsalva maneuver was not controlled for during the upper-body acute RE, which may have independently influenced measures of autonomic modulation and hemodynamics.

Additionally, previous data has shown that hydration status may increase recovery of

HRV measures (Moreno et al., 2013), but this was not controlled for in the present study.

Finally, this study utilized young, moderately active individuals. Therefore, the results of this study may not be applicable to other populations.

In conclusion, this study demonstrates that recovery of vagal modulation measured via HRV and hemodynamics are at least 30 minutes following upper-body acute RE and this response is similar regardless of whether the upper-body acute RE is performed bilaterally or unilaterally. However, recovery of vagal modulation in terms of

HRC was recovered by 30 minutes, which confounds estimation of recovery. Future research may wish to incorporate more sensitive HRC measures, such as SampEn and their responses compared to those of HRV. Additionally, studies should continue to investigate other upper-body acute RE modalities or interventions that may attenuate alterations in measures of autonomic modulation and hemodynamics in addition to sex- specific differences.

CHAPTER V

CHANGES IN PULSE WAVE REFLECTION, CENTRAL ARTERIAL

STIFFNESS, AND BAROREFLEX SENSITIVITY FOLLOWING BILATERAL

AND UNILATERAL UPPER-BODY ACUTE RESISTANCE EXERCISE

Introduction

The current literature suggests that measures of hemodynamics, namely heart rate

(HR) and blood pressure (BP) are increased during recovery from upper-body acute resistance exercise (RE). Further, to illustrate these effects on the cardiovasculature, researchers have supplemented conventional hemodynamics with changes in the shape of the arterial pulse wave (O’Rourke & Pauca, 2004). Changes in the arterial pulse wave following upper-body acute RE may be due to alterations in pulse wave reflection

(Augustine et al., 2018; Fahs et al., 2009; Tai, Marshall, et al., 2018), ventricular function

(Tai, Marshall, et al., 2018), and/or stiffness of the central artery (i.e. aorta) (Augustine et al., 2018; Fahs et al., 2009). Collectively, these measures have been associated with increased risk of cardiovascular disease and events (La Rovere et al., 2001; Pollock et al.,

2000; Weber et al., 2004). Though these risks are likely minimal in young, healthy populations, modalities or interventions that may reduce these alterations are significant, and pertinent.

Measures that quantify changes in pulse wave reflection include the augmentation index (AIx), which describes the extent to which the arterial pulse wave is greater than

68 the initial, forward pulse wave due to the reflected pulse wave, and is determined by the ratio of augmentation pressure (AP) to pulse pressure (PP) (Nichols, 2005). The AIx is largely dependent upon the magnitude and transit time of the reflected pulse wave (Tr)

(Butlin & Qasem, 2017). Further, Tr is suggested to be sensitive to changes in HR, as an elevated HR will result in the reflected pulse wave to return to the heart in diastole, thereby decreasing the AIx (Wilkinson et al., 2000). Thus, the AIx is commonly controlled for at 75 beats per minute (AIx@75). Further, upper-body acute RE may also affect patterns of ventricular function causing changes in the arterial pulse wave. For instance, a decrease in ejection duration (ED) in addition to increases in AP and Tr will increase wasted myocardial work (Ew) (Townsend et al., 2015). Additionally, since the load placed on the left ventricle during ejection is based upon pressure in systole (Butlin

& Qasem, 2017), in the case that pulse wave reflection occurs during systole; the left ventricle is forced to generate increased pressure to cause ejection. This relationship between pressure and time in diastole (DPTI) to systole (SPTI) describes changes in ventricular ejection and is referred to as the subendocardial viability index (SEVR), which is suggested to be indicative of myocardial ischemia (Buckberg et al., 1972).

Changes in the arterial pulse wave following upper-body acute RE may be also be due to changes in tensile stress on the arterial wall. An increase in arterial wall stress generally results in a transfer of force from pliable elastin fibers to stiff collagenous fibers, causing an increase in arterial stiffness (14). These acute increases in arterial stiffness following upper-body acute RE have been reported to occur in the central

69 arteries, namely the aorta (Augustine et al., 2018; Fahs et al., 2009; Okamoto, Masuhara,

& Ikuta, 2009), which may be important given that measures of central arterial stiffness are suggested to be predictive of cardiovascular disease (CVD) related mortality and events (Arnett, Evans, & Riley, 1994; Boutouyrie, Laurent, & Briet, 2008; London &

Cohn, 2002). Additionally, it has also been suggested that there is a significant, negative relationship between central arterial stiffness and baroreflex sensitivity (BRS)

(Heffernan, Collier, et al., 2007; Michas et al., 2012). Specifically, central arterial stiffening may affect the baroreceptors by reducing mechanotransduction and baroreceptor firing (Kingwell et al., 1997), which may precipitate an arrhythmia (La

Rovere et al., 2001). To our knowledge, no studies have reported the effects of upper- body acute RE on BRS. However, it is likely that reductions in central arterial stiffness following upper-body acute RE may reduce BRS.

Upper-body acute RE modalities or interventions that may attenuate these cardiovascular responses are crucial. Currently, one study has suggested that performing the biceps curl, an upper-body exercise, in a bilateral manner produces greater HR and

BP responses compared to when the exercise is performed unilaterally (Moreira et al.,

2017). Specifically, Moreira et al. (2017) reported that unilateral upper-body acute RE consisting of the biceps curl exercise resulted in an attenuated HR and BP response compared to bilateral upper-body acute RE shortly after RE cessation. Therefore, it is plausible that favorable changes in HR and BP following unilateral compared to bilateral upper-body acute RE may occur in parallel to favorable alterations in measures of pulse

70 wave reflection, reduced central arterial stiffness, and increased BRS during recovery.

This study seeks to investigate whether performing acute RE unilaterally might attenuate alterations in HR and BP, measures of pulse wave reflection, central arterial stiffness, and

BRS compared to when the acute RE is performed bilaterally. It was hypothesized that recovery following unilateral upper-body acute RE would attenuate the increase HR and

BP, reduce alterations in measures of pulse wave reflection, as well as attenuate the increase in central arterial stiffness and improve BRS compared to bilateral upper-body acute RE.

Methods

Twenty healthy, moderately active individuals were recruited to participate in this study. Physical activity status was determined using the Lipid Research Clinic questionnaire (Ainsworth et al., 1993). Exclusion criteria included the use of medications or supplements known to affect HR or BP, recent smoking history (< 6 months), obesity

(defined as a BMI ≥ 30 kg/m2), hypertension (resting brachial systolic BP (bSBP) ≥ 130 mmHg or brachial diastolic BP (bDBP) ≥ 80 mmHg), orthopedic problems, open wounds, cancer, known metabolic disease, cardiovascular disease, or renal disease.

These criteria were assessed during the orientation via the Physical Activity Readiness

Questionnaire (PARQ) and Health History Questionnaire. All participants signed a written informed consent prior to the collection of any anthropometric or cardiovascular data. Of the sample of twenty individuals, one individual’s data were excluded from analysis due to a random error in the BP signal, therefore the total number of participants

71 for this study was nineteen. This study was approved by the Institutional Review Board and corresponded to the Declaration of Helsinki.

Following orientation, participants completed four additional visits. During Visit

One, participants were assessed for anthropometrics followed by strength testing on the

5-repetition maximum (5RM) for the bilateral dumbbell (DB) bench press and 10 RM for the DB biceps curl. Visit Two was performed similarly to Visit One but consisted of strength testing on the unilateral DB bench press and unilateral DB biceps curl. Data collection occurred during Visit Three and Visit Four at rest and during recovery from bilateral and unilateral upper-body acute RE that were counterbalanced. All visits were at least 72 hours apart. Measures of HR and BP, central arterial stiffness, BRS, and pulse wave reflection were assessed at rest, 10- and 30-minutes during recovery (Figure 2). All acute exercise visits were collected at the same time of day ( one hour) and occurred between the hours of six a.m. to noon in order to control for diurnal variation.

Participants were asked to abstain from food for at least 3 hours prior to testing as well as caffeine, alcohol, and strenuous exercise for at least 24 hours prior. All women were tested during the early follicular phase of the menstrual cycle (day one through seven) determined by self-report of the first day of their menses.

Height and weight were assessed using a stadiometer and balance beam scale

(Detecto 448; Cardinal Scale Manufacturing, Web City, MO, USA), respectively. The participant’s height was measured to the nearest tenth of a centimeter and weight to the nearest tenth of a pound (lb) which was converted to kilograms to calculate BMI.

Prior to maximal testing, participants completed a 5-minute warm-up at a self- selected pace on the cycle ergometer (Schwinn Air Dyne; Boulder, Colorado, USA).

Strength testing at the 5RM on the DB bench press and 10RM on the DB biceps curl was carried out using methods previously described (Harman et al., 2000). In short, participants completed two sub-maximal warm-up sets. In the first set, participants completed approximately 10 repetitions. Prior to set two, the weight of the DBs was increased 5 to 10% and participants were instructed to complete 3 to 5 repetitions.

Thereafter, weight was increased 5 to 10% each set until the participant could no longer complete the assigned repetitions or maintain set cadence. The unilateral upper-body acute RE testing was completed in both the left and right arm. Participants were given five sets to obtain the 5RM and 10RM for respective exercises through a full range of motion with 2 minutes of rest between sets and exercises. Cadence was set at a two-one- two duty cycle for all repetitions (two-second concentric, one-second pause, and two- second eccentric (Fahs et al., 2009). The same spotter was present at all testing sessions to ensure the safety of the participants during testing.

Prior to the start of data collection, participants were prepped with a 3-lead electrocardiogram (ECG) then rested quietly in the supine position in a dimly lit, temperature-controlled (19-22C) laboratory for 10 minutes. Following, brachial BP was assessed using an automated oscillometric cuff placed on the right arm (AtCor Medical,

SphygmoCor EXCEL Technology, Sydney, Australia). Brachial measurements were made in duplicate, until two values were within five mmHg of each other for both bSBP

73 and bDBP. Approximately one minute was given between BP assessments. The two values within five mmHg of each other were then averaged and later used to calibrate the brachial signal with the measured brachial arterial pressure wave. If the two values were not within five mmHg, a third reading was taken. The brachial PP (bPP) was calculated as bSBP minus bDBP. Following, the brachial pulse wave was applanated to assess measures of pulse wave reflection through a valid transfer function (15). This method has been reported to be reliable and has been validated against traditional invasive measurement (Takazawa et al., 1996). Measures of pulse wave reflection included central SBP (cSBP), central DBP (cDBP), AIx, AIx@75, AP, central pulse pressure

(cPP), Tr, Ew, DPTI, SPTI, and SEVR. Myocardial work was calculated using the equation:

Ew = 1.333 x AP (ED - Tr) x (π / 4) (1) where 1.333 is the conversion factor for mmHg/s to dynes-seconds/cm2 (17).

Central arterial stiffness was assessed via carotid-femoral pulse wave velocity (cf-

PWV) (Townsend et al., 2015) utilizing applanation tonometry (AtCor Medical,

SphygmoCor EXCEL Technology, Sydney, Australia). Specifically, cf-PWV was calculated by measuring the difference of the foot-to-foot transit time of the pulse wave from the right common carotid artery and right femoral pulse, and dividing it by the estimated length of the aortic path (Butlin & Qasem, 2017). A single, high fidelity transducer was placed on right common carotid artery in addition to an automated cuff on the most proximal portion of the right leg to measure pressure waveforms over a 10

74 second epoch. The distances of the waveforms, which reflect the aortic path, were obtained via straight line tape measurement from the right common carotid artery to the right femoral artery using the subtraction method (Butlin & Qasem, 2017). Each measurement was made in duplicate, with no more than a tenth of a m/s difference between readings.

Continuous ECG and BP recordings were obtained from the middle finger of the left hand using photoplethysmography (Human Non-Invasive BP (NIBP) Nano; AD

Instruments, Colorado Springs, CO, USA). HR and BP signals were collected via

PowerLab data acquisition and LabChart software (AD instruments, Colorado Springs,

CO, USA) and sampled at 1000 and 200 Hertz (Hz), respectively. Any ectopic beats, noise, and artifacts on the ECG were manually replaced with interpolated adjacent R wave values (Buchheit et al., 2007). Following, HR and BP signals were imported into

WinCPRS for analysis (Absolute Aliens, Turku, Finland). Spontaneous BRS was assessed using the Sequence Method. This was determined from the beat-to-beat changes in the pulse interval (PI) and SBP. Any occurrence of three or more consecutive heartbeats in which the PI and SBP changed in the same direction up (+SBP/+PI), or down (-SBP/-PI) were recorded. The threshold change was set at five milliseconds for

PIs and one mmHg for SBP. Only sequences with correlations ≥0.80 were accepted. All data were collected following previously reported recommendations (Parati et al., 1988).

The upper-body acute RE protocol completed in the present study was adapted from that of (Fahs et al., 2009), which demonstrated increases in measures of central

75 arterial stiffness in a analogous population to the present study in terms of age and physical activity status. In addition, participants in the present study performed a protocol that was similar for RE volume, rest period length, and cadence with the exception that DBs were used instead of a barbell in order to accommodate the unilateral modality. Following collection of resting measures, participants completed a 5-minute warm-up on the cycle ergometer and then a warm-up on the DB bench press wat 50% of their 5 RM for 10 repetitions. Participants then completed four sets of five repetitions at their 5 RM. The same warm-up procedure was given for the DB biceps curl, followed by

4 sets of 10 repetitions at the 10 RM. If participants could not complete the given repetitions, a drop set begun whereby weight was decreased by 2.2 kg per limb until the participant could complete the 5 or 10 repetitions with proper form and cadence.

Participants were given two minutes of rest between sets and exercises during both the bilateral and unilateral upper-body acute RE. During unilateral upper-body acute RE, participants randomly performed the repetitions in either the right or left limb first. After the fifth repetition, the rest period began, and participants were given approximately two minutes of rest prior to performing the next set of repetitions in the same limb. This rest period procedure was followed to match time-under-tension between bilateral and unilateral modalities. Cadence was set at two-one-two duty cycle for all repetitions.

Statistical Analyses

All data were checked for extreme outliers and assumptions of Analysis of

Variance (ANOVA) IBM SPSS Version 21 (Armonk, NY, USA). Normality was

76 assessed according to Shapiro-Wilk tests. Violations of sphericity were corrected utilizing a Greenhouse-Geisser correction. Independent samples-tests were conducted in order to determine anthropometric differences between men and women. Additionally, paired samples-tests were conducted in order to determine differences in total workload within upper-body acute RE conditions. Following, 2x3 Repeated Measures ANOVAs were used to examine the differences across conditions (bilateral, unilateral) and time

(Rest, 10-minutes, 30-minutes post-exercise) on hemodynamics (HR, bSBP, bDBP, and bPP), pulse wave reflection (cSBP, cDBP, AIx, AIx@75, AP, cPP, Tr, Ew, DPTI, SPTI, and SEVR), central arterial stiffness (cf-PWV), and BRS (+SBP/+PI, -SBP/-PI). If the

ANOVA indicated a significant interaction, paired-tests were conducted post hoc with a

Holm-Bonferroni correction factor (Holm, 1979). All results were presented as mean  standard deviation. Sample size was calculated using G*Power version 3.1.9.2 (Faul et al., 2009). The sample size of the present study was based on data collected by

Augustine et al. (2018) whereby rest and post-exercise means and standard deviations of cPP were used to calculate an effect size of 0.39. A sample size of 13 participants completing each condition, was estimated to achieve a power of 80%, and an alpha of

0.05.

Results

Participant characteristics are represented in Table 4. Men were significantly (p 

0.001) heavier and taller compared to women.

Table 4 Participant characteristics (N = 19).

Characteristic Men (N = 9) Women (N = 10)

Age (yr) 23 ± 3 23 ± 3

Height (m) 1.8 ± 0.1§ 1.7 ± 0.0

Weight (kg) 81.9 ± 10.1§ 66.8 ± 10.7

BMI (kg•m2) 25.9± 3.0 24.5 ± 3.0

BMI, body mass index; Data presented are mean ± SD. §Significantly different from women (p  0.001).

There was no significant (p > 0.05) difference in total workload between the bilateral and unilateral upper-body acute RE condition (Table 5). Further, there were no significant (p > 0.05) condition by time interactions for any dependent variables.

Table 5 Upper-body acute resistance exercise (RE) condition workload (N = 19).

Condition

Bilateral BP (kg) 2189 ± 954

Bilateral BC (kg) 1996 ± 820

R, Unilateral BP (kg) 2105 ± 1081

L, Unilateral BP (kg) 2218 ± 1039

R, Unilateral BC (kg) 1996 ± 821

L, Unilateral BC (kg) 1886 ± 744

BP, Bench Press; BC, Biceps Curl; R, Right Arm; L, Left Arm; Data presented are mean ± SD.

2 There were significant main effects of time for HR (p  0.001, np = 0.72) and

2 2 bDBP (p  0.001, np = 0.59) and bPP ( p  0.006), np = 0.24), but no significant main effect of time for bSBP (p > 0.05) following bilateral and unilateral upper-body acute RE

(Table 6). There was a significant increase in HR at all time points compared to Rest.

Further, HR significantly decreased from 10 to 30 minutes, but remained above Rest.

Additionally, there was a significant decrease in bDBP at 10 and 30 minutes compared to

Rest, in addition to a significant increase in bDBP from 10 to 30 minutes, which

79 remained below Rest. Lastly, the bPP was augmented at 10 minutes during recovery, but was recovered by 30 minutes.

Table 6

Measures of heart rate and blood pressure at rest and during recovery from bilateral and unilateral upper-body acute resistance exercise in moderately active individuals (N =

19).

Bilateral Unilateral

Rest 10 minutes 30 minutes Rest 10 minutes 30 minutes

HR (bpm) 56  5 67  9* 62  9*† 55  8 67  12* 63  10*† bSBP (mmHg) 115  7 114  9 113  7 115  7 114  8 116  8 bDBP (mmHg) 64  5 61  5* 63  4*† 67  5 63  5* 66  5*† bPP, (mmHg) 50  8 53  9* 51  7 47  5 52  8* 50  7 bDBP, Brachial Diastolic Blood Pressure; bSBP, Brachial Systolic Blood Pressure; HR, Heart Rate. Data are mean ± standard deviation. *p ≤ 0.01, significantly different from Rest; †p ≤ 0.01, significantly different from 10 minutes.

2 There were significant main effects of time for cDBP (p  0.001, np = 0.57), AIx

2 2 2 (p  0.001, np = 0.62), AIx@75 (p  0.001, np = 0.77), AP (p  0.001, np = 0.46, cPP (p

2 2 2  0.001, np = 0.61), Ew (p  0.001, np = 0.7), DPTI (p  0.001, np = 0.7), SPTI (p 

2 2 0.001, np = 0.46), and SEVR (p  0.001, np = 0.66) (Table 7). There were no significant main effects of time for cSBP or Tr (p > 0.05). Following bilateral and unilateral upper-

80 body acute RE, there was a significant decrease in cDBP, DPTI, and SEVR such that they were decreased at both 10 and 30 minutes compared to Rest. However, there a significant increase in cDBP, DPTI, and SEVR from 10 to 30 minutes such that it remained below Rest. Additionally, there was a significant increase in AP, AIx,

AIx@75bpm, SPTI, and Ew such that they were significantly increased at 10 and 30 minutes compared to Rest. The cPP was also significantly increased, but only at 10 minutes compared to Rest. Further, there was a significant decrease in AP, AIx,

AIx@75bpm, Ew, and SPTI from 10 to 30 minutes. Though, these measures significantly decreased from 10 to 30 minutes such that they were similar to Rest.

81 Table 7

Measures of pulse wave reflection at rest and during recovery from bilateral and unilateral upper-body acute resistance exercise in moderately active individuals (N = 19). Bilateral Unilateral

Rest 10 minutes 30 minutes Rest 10 minutes 30 minutes cSBP (mmHg) 1006 1017 996 1016 1027 1017 cDBP (mmHg) 655 625* 644*† 695 645* 675*†

AIx (%) 79 2413* 1813*† 116 2513* 149*†

AIx@75 (%) 210 2216* 913*† 27 2415* 1013*†

AP (mmHg) 44 97* 75*† 42 106* 54*† cPP (mmHg) 356 396* 355† 324 397* 355†

Tr (ms) 149.15.2 147.97.2 147.16.4 149.74.5 147.45.9 149.65.4

2 Ew (dynes/cm ) 695.2559.9 1419.6947* 1055.1681.9*† 646400.8 1525.4930.9* 897.4647.8*†

DPTI (ms) 2862.6151.3 2540.7165.5* 2706.7 207.6*† 2964.8259.5 2630.82274.5* 2775.1238.6*†

SPTI (ms) 1794.4207.6 2090.7324.8* 1926.8 288.3*† 1829.7333.6 2095.1 336.3* 2005.5319.0*†

SEVR 161.518.8 124.923.2* 145.1 31.2*† 165.3 32.2 129.5 28.4* 142.930.0*†

82 AIx, Augmentation Index; AIx@75, Augmentation Index Normalized to 75bpm; cAP, Central Augmentation Pressure; cDBP, Central Diastolic Blood

Pressure; cSBP, Central Systolic Blood Pressure; DPTI, Diastolic Pressure Time Index; SEVR, Subendocardial Viability Ratio; SPTI, Systolic Pressure

Time Index; Ew, Wasted Left Ventricular Energy. Data are mean ± standard deviation. *p ≤ 0.001, significantly different from rest; †p ≤ 0.001, significantly different from 10 minutes.

2 There was a significant main effect of time for cf-PWV (p = 0.002, np = 0.29) following bilateral and unilateral upper-body acute RE (Table 8). Specifically, it was significantly increased at 10 minutes compared to Rest. Further, cf-PWV significantly decreased from 10 to 30 minutes, such that it was similar to Rest

Table 8

Central arterial stiffness at rest and during recovery from bilateral and unilateral upper- body acute resistance exercise in moderately active individuals (N = 19).

Bilateral Unilateral

Rest 10 minutes 30 minutes Rest 10 minutes 30 minutes

Cf-PWV (m/s) 5.5  0.6 5.8  0.7* 5.6  0.6† 5.7  0.7 5.9  0.5* 5.8  0.6†

Cf-PWV, carotid-femoral pulse wave velocity; Data presented are mean ± SD. *p ≤ 0.001, significantly different from Rest; †p ≤ 0.001, significantly different from 10 minutes.

There were significant main effects of time for +SBP/+PI and -SBP/-PI (p 

2 0.001, np = 0.35) following bilateral and unilateral upper-body acute RE (Table 9).

Specifically, there was a significant increase in +SBP/+PI at 10 and 30 minutes compared to Rest. Additionally, there was a significant increase in -SBP/-PI at 30 minutes compared to Rest.

Table 9.

Measures of baroreflex sensitivity at rest and during recovery from bilateral and unilateral upper-body acute resistance exercise in moderately active individuals (N =

19).

Bilateral Unilateral

Rest 10 minutes 30 minutes Rest 10 minutes 30 minutes

+ SBP/ +PI 7  7 13  8* 13  8* 9 6 15  8* 16  10*

- SBP/ -PI 9  9 12  8 15  9* 9  7 13  8 16  9*

SBP, Systolic Blood Pressure; PI, Pulse Interval. Note: The plus (+) sign denotes an increase whereas the minus (-) sign denotes a decrease in the SBP/PI. *p ≤ 0.001, significantly different from Rest; †p ≤ 0.001, significantly different from 10 minutes.

Discussion

This study sought to investigate the effects of bilateral and unilateral upper-body acute RE on HR and measures of BP, pulse wave reflection, central arterial stiffness, and

BRS, in young, moderately active individuals. The primary findings of the present study disagree with the preliminary hypotheses that unilateral upper-body acute RE would attenuate alterations in these measures. Instead, this study suggests that bilateral and unilateral upper-body acute RE produce similar increases in HR and decreases in DBP.

These conventional BP measures were also altered with those of pulse wave reflection, central arterial stiffness, and BRS. Specifically, measures of pulse wave reflection,

specifically AIx, AP, cPP, Ew, and SPTI were increased, whereas cDBP, DPTI and

SEVR were decreased during recovery from upper-body acute RE thereby suggesting increases in wave reflection and myocardial work. Further, both upper-body acute RE modalities increased central arterial stiffness while reducing BRS suggesting stiffness of the aorta. Collectively, this study suggests that recovery from bilateral and unilateral upper-body acute RE in terms of measures of hemodynamics and pulse wave reflection are at least 30 minutes and those of central arterial stiffness and BRS are at least 10 and

30 minutes, respectively.

Although there were no differences in measures between the bilateral and unilateral upper-body acute RE, the present study is in agreement with the current literature which suggests significant increases in HR and bPP (Augustine et al., 2018;

Fahs et al., 2009), following upper-body acute RE. However, this study reported no change in bSBP and a decrease bDBP, which is not a universal response (Fahs et al.,

2009; Tai, Marshall, et al., 2018). For example, though Fahs et al. (2009) and Augustine et al. (2018) reported a decrease in bDBP at ~15 and 10 minutes, respectively during recovery, there was also a reported increase in bSBP. This difference could be attributed to what appears to be a greater RE load in that of Fahs et al. (2009) compared to the present study. Load was not reported by Augustine et al. (2018), which limits our ability to make true comparisons. These discrepancies are important as previous literature has shown that RE load may independently influence the magnitude of the BP response

(Rezk, Marrache, Tinucci, Mion, & Forjaz, 2006). Similarly, this may further explain

86 why (Tai, Marshall, et al., 2018), who utilized only one upper-body RE (i.e. bench press), did not observe a change in either bSBP or bDBP. Collectively, studies suggest that both load and the number of exercises performed may affect changes in hemodynamics.

In terms of pulse wave reflection, the current study reported no change in cSBP, but a significant decrease in cDBP for at least 30 minutes. These specific measures, which reflect aortic BP were not reported by Fahs et al. (2009). However, Augustine et al. (2018) suggests that cDBP is reduced for up to 20 minutes following cessation of upper-body acute RE. Differential findings could stem from the fact that the present study utilized both men and women, whereas Augustine et al. (2018) utilized only women. Though sex differences have not been conclusively demonstrated in the literature at this point for measures of pulse wave reflection, there is still sufficient evidence to suggest that differences in estrogen levels amongst sexes influence the cardiovasculature (Bechlioulis et al., 2010). Further, this study included women who were either taking or not taking oral contraceptives whereas, Augustine et al. (2018) only included women who were not taking any form of oral contraceptive. Some have suggested that oral contraceptives influence C-Reactive Protein by increasing vascular tone (van Rooijen et al., 2006). It is plausible that this may explain why women in the present study demonstrated a longer reduction in cDBP, which is dissimilar to Augustine et al. (2018), but this is beyond the scope of this study.

Increases in other measures of pulse wave reflection such as AIx, AIx@75, AP and were also similar to studies previously mentioned. Fahs et al. (2009) and Augustine

87 et al. (2018) reported increases in the AIx at ~15 minutes and 10 minutes, respectively.

Additionally, Fahs et al. (2009) also reported an increase in the AIx@75 for up to 30 minutes, which was not reported by Augustine et al. (2018). These differences in recovery of the AIx are likely the result of differences in AP, which was augmented at all time points in the present study. Augustine et al. (2018) also reported an increase in the

AP, but this was recovered by 30 minutes. The AP was not reported by Fahs et al.

(2009). Further, cPP was increased for at least 10 minutes in the present study, which has not been previously demonstrated. Augustine et al. (2018) instead reported a slight decrease in cPP at 30 minutes. In addition, (Tai, Marshall, et al., 2018) also did not report an increase in cPP. However, one of the main determinants of cPP is suggested to be central arterial stiffness (Stergiopulos & Westerhof, 1998), which may further elucidate the findings of the present study. Measures of central arterial stiffness were not reported by that of (Tai, Marshall, et al., 2018). Therefore, discrepancies could be attributed to differential changes in arterial stiffness, but this cannot be determined.

Further, there were significant alterations in left ventricular function following the upper-body acute RE. Changes in these measures within the literature are limited.

However, (Tai, Marshall, et al., 2018) also reported an increase in Ew , decrease in

DPTI, and increase in SPTI, thus an overall decrease in SEVR for at least 10 minutes during recovery. This study further suggests that recovery of these measures is at least 30 minutes, but future studies should further extend the timeline of data collection to determine time to recovery.

As earlier stated the upper-body acute RE protocol in the present study was designed similarly to that of Fahs et al. (2009) and Augustine et al. (2018), with the exception that dumbbells were used instead of the barbell and EZ curl bar in order to accommodate the unilateral RE condition. These authors also reported an increase in central arterial stiffness, but at ~15 minutes following cessation of the upper-body acute

RE in moderately active men. Comparably, Augustine et al. (2018) also reported an increase in central arterial stiffness for up to 30 minutes utilizing recreationally active women. However, in this study women performed 10 total working sets compared to 8 in the present study and that of Fahs et al. (2009). It is likely that the increased volume of work and time-under-tension in the study by Augustine et al. (2018) increased time to recovery, but this is speculation. Nevertheless, the present study further contributes to the existing literature regarding the effects of upper-body acute RE on central arterial stiffness.

As hypothesized, there were significant reductions in BRS that occurred in parallel with increases in central arterial stiffness. However, according to the results of the present study it appears that recovery of the baroreflex is longer duration. Though the reason for these differences is unclear, the material properties of the carotid and aorta are structurally different such that the carotid considered a more muscular artery (Safar,

Blacher, Mourad, & London, 2000). It has been suggested that arteries possessing more musculature experience greater functional effects (i.e. wall stress, sympathetic tone), which may explain these differences. Furthermore, it is likely that rapid resetting of the

89 baroreflex in conjunction with post-excitatory depression also contributed to greater time to recovery (Chapleau, Li, Meyrelles, Ma, & Abboud, 2001). The findings in the present regarding BRS are novel as no other study has reported these measures following upper- body acute RE alone. Nevertheless, a few studies have examined changes in BRS following whole-body acute RE and also propose that BRS is reduced for at least 20 to 30 minutes (Heffernan, Collier, et al., 2007; Kingsley et al., 2018). Moreover, it is clear that more research is needed to fully elucidate the effects and recovery of the baroreflex following upper-body acute RE.

The premise of this study is largely based upon the study by Moreira et al. (2017) who previously reported that unilateral upper-body acute RE conferred lesser cardiovascular responses compared to bilateral upper-body acute RE. However, the present study does not support this hypothesis as there were no significant differences between the two conditions. Instead there were similar increases in HR and decreases in

BP during recovery, which seemed to prompt similar increases in central arterial stiffness, decreases in BRS, and alterations in pulse wave reflection. Discrepancies between the present study and that of Moreira et al. (2017) may be attributed to differences in the upper-body acute RE protocol. In the study by Moreira et al. (2017) individuals only performed the biceps curl for 3 sets of 10 repetitions at the 80% of the

10RM. The smaller muscle group utilized in this study and the lower RE volume may explain differences compared to the present study. Additionally, the present study included the bench press exercise in addition to the biceps curl. It is plausible that the

90 bench press exercise itself, which is closer in proximity to the heart may have alone produced the similar alterations between the two conditions, but this is unknown.

There are a few limitations to the present study. First, this study included both men and women, such that men were taller and heavier. However, these characteristics were not utilized as a covariate due to their lack of linearity with the dependent variables.

The fact that height especially had no effect on measures of cf-PWV may be significant considering length of the aorta plays a direct influence in its’ assessment. Further, there are considerable hormonal differences between men and women, such that women have inherently higher levels of estrogen, which is cardioprotective. Unfortunately, sex differences could not be determined in this study due to insufficient power. Second, breathing technique was not controlled for (i.e. Valsalva maneuver) and this has been suggested to independently influence central arterial stiffness (Heffernan, Jae, Edwards, et al., 2007). Lastly, we did not perform a dietary recall prior to data collection.

Although participants were asked to refrain from food for at least three hours prior to testing, some studies have suggested that a high fat meal may result in changes in central arterial stiffness and pulse wave reflection for ~four hours (Lithander et al., 2013). Thus, future studies may wish to perform dietary recall or standardize meals prior to collection of cardiovascular measures such as those in the present study.

In conclusion, both bilateral and unilateral upper-body acute RE result in similar increases in central arterial stiffness for at least 10 minutes, as well as increases in HR and BP, reductions in BRS, and changes in pulse wave reflection for at least 30 minutes.

The present study further contributes to the literature regarding upper-body acute RE and its effects on the cardiovasculature, which unmistakably warrants further research given the relationship of these variables to CVD and CVD-related events, as well as alterations in the heart period such as arrhythmia. Lastly, studies should continue to investigate other upper-body acute RE modalities or interventions that may attenuate these alterations and whether there are differences between men and women.

CHAPTER VI

SUMMARY

The purpose of the present study was to determine whether bilateral and unilateral upper-body acute RE mediated different cardiovascular responses in terms of hemodynamics, pulse wave reflection, central arterial stiffness, autonomic modulation and baroreflex sensitivity. Previous literature has demonstrated that unilateral upper- body acute RE reduced cardiovascular alterations in terms of HR and brachial BP. It was hypothesized that these previous findings may be true of other cardiovascular measures, which may be significant considering their relationship with CVD and CVD-related events. However, the results of the present study do not support previous findings that unilateral upper-body acute RE confers different responses to that of bilateral upper-body acute RE in terms of HR and BP. Further, there were no differences in other cardiovascular measures, namely pulse wave reflection, central arterial stiffness, autonomic modulation and baroreflex sensitivity. Therefore, the present study suggests that bilateral and unilateral upper-body acute RE result in similar cardiovascular alterations. Nevertheless, upper-body acute RE does significantly alter hemodynamics, pulse wave reflection, central arterial stiffness, autonomic modulation and baroreflex sensitivity during the recovery period.

The physiological mechanisms mediating these responses in the upper body are unclear. However, these changes may have originated from the intermittent increases in

BP during performance of the upper-body acute resistance exercise. It is plausible that

93 these increases may have altered the arterial pulse wave mainly via augmentation and changes in the reflected pulse wave, which was demonstrated in the present study.

Further, changes in the arterial pulse wave seemed to prompt an increase in myocardial work, and thus ischemia. Further, the upper-body acute resistance exercise may have altered mechanical properties of the aorta through a shift in load-bearing capacity from elastic to collagenous fibers, the latter which is inherently stiffer. These transient increases in aortic stiffness may have in turn altered those of autonomic modulation and baroreflex sensitivity. Specifically, stiffening of the aorta and common carotid artery likely reduced baroreceptor firing resulting in sustained vagal withdrawal during the recovery period. Moreover, it is clear that upper-body acute resistance exercise alters the cardiovasculature during the recovery period, which may be of importance for the general population and athletes, as well as health and strength and conditioning professionals whom are prescribing resistance exercise.

The implications of the current findings suggest an increased cardiovascular risk during the recovery period (i.e. arrythmia, stroke, etc.). However, the likelihood of these risks occurring in healthy populations is unclear. Nevertheless, given the worldwide presence of cardiovascular disease that continues to increase, prevention is of utmost importance. Many health professionals prescribe resistance exercise to improve health and well-being, however these benefits may only be in terms of muscular fitness, and not that of the cardiovasculature. Therefore, it is imperative that future research continue to

94 investigate resistance exercise, particularly in the upper-body and its’ effects on cardiovascular health.

APPENDICES

APPENDIX A

INFORMED CONSENT

APPENDIX A Informed Consent

100

101

APPENDIX B

PHYSICAL ACTIVITY READINESS QUESTIONNAIRE

Appendix B

Physical Activity Readiness Questionnaire

103

APPENDIX C

HEALTH HISTORY QUESTIONNAIRE

Appendix C

Health History Questionnaire

105

APPENDIX D

LIPID RESEARCH CLINICS QUESTIONNAIRE

Appendix D

Lipid Clinics Research Questionnaire

107

108

APPENDIX E

ANTHROPOMETRICS

Appendix E

Anthropometrics

110

APPENDIX F

MAXIMAL STRENGTH TESTING

Appendix F

Maximal Strength Testing

112

APPENDIX G

DATA COLLECTION

Appendix G

Data Collection

114 115

APPENDIX H

LIKERT AND VISUAL ANALOG SCALE

APPENDIX H

Likert And Visual Analog Scale

117

REFERENCES

119

REFERENCES

Ainsworth, B. E., Jacobs, D. R., Jr., & Leon, A. S. (1993). Validity and reliability of self-

reported physical activity status: the Lipid Research Clinics questionnaire.

Medicine and Science in Sports and Exercise, 25(1), 92-98. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/8423761

Albert, C. M., Mittleman, M. A., Chae, C. U., Lee, I. M., Hennekens, C. H., & Manson,

J. E. (2000). Triggering of sudden death from cardiac causes by vigorous exertion.

New England Journal of Medicine, 343(19), 1355-1361.

doi:10.1056/NEJM200011093431902

American College of Sports, M. (2009). American College of Sports Medicine position

stand. Progression models in resistance training for healthy adults. Medicine and

Science in Sports and Exercise, 41(3), 687-708.

doi:10.1249/MSS.0b013e3181915670

Armentano, R. L., Levenson, J., Barra, J. G., Fischer, E. I., Breitbart, G. J., Pichel, R. H.,

& Simon, A. (1991). Assessment of elastin and collagen contribution to aortic

elasticity in conscious dogs. American Journal of Physiology, 260(6 Pt 2), H1870-

1877. doi:10.1152/ajpheart.1991.260.6.H1870

Arnett, D. K., Evans, G. W., & Riley, W. A. (1994). Arterial stiffness: a new

cardiovascular risk factor? American Journal of Epidemiology, 140(8), 669-682.

doi:10.1093/oxfordjournals.aje.a117315

120

Augustine, J. A., Nunemacher, K. N., & Heffernan, K. S. (2018). Menstrual phase and

the vascular response to acute resistance exercise. European Journal of Applied

Physiology, 118(5), 937-946. doi:10.1007/s00421-018-3815-1

Bailey, A. J. (2001). Molecular mechanisms of ageing in connective tissues. Mechanisms

of Ageing and Development, 122(7), 735-755. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/11322995

Bechlioulis, A., Naka, K. K., Calis, K. A., Makrigiannakis, A., Michalis, L., &

Kalantaridou, S. N. (2010). Cardiovascular effects of endogenous estrogen and

hormone therapy. Current Vascular Pharmacology, 8(2), 249-258. Retrieved

from https://www.ncbi.nlm.nih.gov/pubmed/19485910

Billman, G. E., & Hoskins, R. S. (1989). Time-series analysis of heart rate variability

during submaximal exercise. Evidence for reduced cardiac vagal tone in animals

susceptible to ventricular fibrillation. Circulation, 80(1), 146-157. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/2567640

Bogert, L. W., & van Lieshout, J. J. (2005). Non-invasive pulsatile arterial pressure and

stroke volume changes from the human finger. Experimental Physiology, 90(4),

437-446. doi:10.1113/expphysiol.2005.030262

Boudoulas, H., Rittgers, S. E., Lewis, R. P., Leier, C. V., & Weissler, A. M. (1979).

Changes in diastolic time with various pharmacologic agents: implication for

myocardial perfusion. Circulation, 60(1), 164-169.

doi:doi:10.1161/01.CIR.60.1.164

121

Boutouyrie, P., Laurent, S., & Briet, M. (2008). Importance of arterial stiffness as

cardiovascular risk factor for future development of new type of drugs.

Fundamental and Clinical Pharmacology, 22(3), 241-246. doi:10.1111/j.1472-

8206.2008.00584.x

Brozek, J., Grande, F., Anderson, J. T., & Keys, A. (1963). Densitometric analysis of

body composition: Revision of some quantitative assumptions. Annals of the New

York Academy of Sciences, 110, 113-140. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/14062375

Buchheit, M., Laursen, P. B., & Ahmaidi, S. (2007). Parasympathetic reactivation after

repeated sprint exercise. American Journal of Physiology: Heart and Circulatory

Physiology, 293(1), H133-141. doi:10.1152/ajpheart.00062.2007

Buckberg, G. D., Fixler, D. E., Archie, J. P., & Hoffman, J. I. (1972). Experimental

subendocardial ischemia in dogs with normal coronary arteries. Circulation

Research, 30(1), 67-81. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/5007529

Buckwalter, J. B., & Clifford, P. S. (2001). The paradox of sympathetic vasoconstriction

in exercising skeletal muscle. Exercise and Sport Sciences Reviews, 29(4), 159-

163. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11688788

Butlin, M., & Qasem, A. (2017). Large Artery Stiffness Assessment Using SphygmoCor

Technology. Pulse 4(4), 180-192. doi:10.1159/000452448

122

Casey, D. P., Curry, T. B., Joyner, M. J., Charkoudian, N., & Hart, E. C. (2011).

Relationship between muscle sympathetic nerve activity and aortic wave

reflection characteristics in young men and women. Hypertension, 57(3), 421-

427. doi:10.1161/HYPERTENSIONAHA.110.164517

Chapleau, M. W., Li, Z., Meyrelles, S. S., Ma, X., & Abboud, F. M. (2001). Mechanisms

determining sensitivity of baroreceptor afferents in health and disease. Annals of

the New York Academy of Sciences, 940, 1-19. doi:10.1111/j.1749-

6632.2001.tb03662.x

Collier, S. R., Diggle, M. D., Heffernan, K. S., Kelly, E. E., Tobin, M. M., & Fernhall, B.

(2010). Changes in arterial distensibility and flow-mediated dilation after acute

resistance vs. aerobic exercise. Journal of Strength and Conditioning Research,

24(10), 2846-2852. doi:10.1519/JSC.0b013e3181e840e0

Collins, H. L., Augustyniak, R. A., Ansorge, E. J., & O'Leary, D. S. (2001). Carotid

baroreflex pressor responses at rest and during exercise: cardiac output vs.

regional vasoconstriction. American Journal of Physiology: Heart and

Circulatory Physiology, 280(2), H642-648.

doi:10.1152/ajpheart.2001.280.2.H642

Coote, J. H., Hilton, S. M., & Perez-Gonzalez, J. F. (1971). The reflex nature of the

pressor response to muscular exercise. Journal of Physiology, 215(3), 789-804.

Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/5090995

123

De Freitas, M. C., Ricci-Vitor, A. L., Quizzini, G. H., de Oliveira, J., Vanderlei, L. C. M.,

Lira, F. S., & Rossi, F. E. (2018). Postexercise hypotension and autonomic

modulation response after full versus split body resistance exercise in trained

men. J Exerc Rehabi, 14(3), 399-406. doi:10.12965/jer.1836136.068

Dobrin, P. B., & Rovick, A. A. (1969). Influence of vascular smooth muscle on

contractile mechanics and elasticity of arteries. American Journal of Physiology,

217(6), 1644-1651. doi:10.1152/ajplegacy.1969.217.6.1644

Domanski, M. J., Davis, B. R., Pfeffer, M. A., Kastantin, M., & Mitchell, G. F. (1999).

Isolated systolic hypertension : prognostic information provided by pulse

pressure. Hypertension, 34(3), 375-380. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/10489379

Fahs, C. A., Heffernan, K. S., & Fernhall, B. (2009). Hemodynamic and vascular

response to resistance exercise with L-arginine. Medicine and Science in Sports

and Exercise, 41(4), 773-779. doi:10.1249/MSS.0b013e3181909d9d

Faul, F., Erdfelder, E., Buchner, A., & Lang, A. G. (2009). Statistical power analyses

using G*Power 3.1: tests for correlation and regression analyses. Behavior

Research Methods, 41(4), 1149-1160. doi:10.3758/BRM.41.4.1149

Feigenbaum, M. S., & Pollock, M. L. (1999). Prescription of resistance training for health

and disease. Medicine and Science in Sports and Exercise, 31(1), 38-45.

Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9927008

124

Figueiredo, T., Rhea, M. R., Peterson, M., Miranda, H., Bentes, C. M., dos Reis, V. M.,

& Simao, R. (2015). Influence of number of sets on blood pressure and heart rate

variability after a strength training session. Journal of Strength and Conditioning

Research, 29(6), 1556-1563. doi:10.1519/JSC.0000000000000774

Fokkema, D. S., VanTeeffelen, J. W., Dekker, S., Vergroesen, I., Reitsma, J. B., &

Spaan, J. A. (2005). Diastolic time fraction as a determinant of subendocardial

perfusion. American Journal of Physiology-Heart and Circulatory Physiology,

288(5), H2450-H2456.

Franklin, S. S., Wong, N. D., Larson, M. G., & Levy, D. (1999). Is pulse pressure useful

in predicting risk for coronary heart Disease? The Framingham heart study.

Circulation (1524-4539 ).

Gift, A. G. (1989). Visual analogue scales: measurement of subjective phenomena.

Nursing Research, 38(5), 286-288. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/2678015

Goldberger, A. L. (1991). Is the normal heartbeat chaotic or homeostatic? News in

Physiological Sciences, 6, 87-91. doi:10.1152/physiologyonline.1991.6.2.87

Goldberger, A. L., Bhargava, V., West, B. J., & Mandell, A. J. (1985). On a mechanism

of cardiac electrical stability. The fractal hypothesis. The Biophysical Journal,

48(3), 525-528. doi:10.1016/S0006-3495(85)83808-X

Goldberger, A. L., Rigney, D. R., Mietus, J., Antman, E. M., & Greenwald, S. (1988).

Nonlinear dynamics in sudden cardiac death syndrome: heartrate oscillations and

125

bifurcations. Experientia, 44(11-12), 983-987. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/3197810

Haennel, R. G., Snydmiller, G. D., Teo, K. K., Greenwood, P. V., Quinney, H. A., &

Kappagoda, C. T. (1992). Changes in blood pressure and cardiac output during

maximal isokinetic exercise. Archives of Physical Medicine and Rehabilitation,

73(2), 150-155. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/1543410

Halliwill, J. R., Taylor, J. A., & Eckberg, D. L. (1996). Impaired sympathetic vascular

regulation in humans after acute dynamic exercise. Journal of Physiology, 495 (

Pt 1), 279-288.

Harman, E., Carhammer, J., & Pandorf, C. (2000). Essentials of Strength and

Conditioning. Champaign, IL: Human Kinetics.

Heffernan, K. S., Collier, S. R., Kelly, E. E., Jae, S. Y., & Fernhall, B. (2007). Arterial

stiffness and baroreflex sensitivity following bouts of aerobic and resistance

exercise. International Journal of Sports Medicine, 28(3), 197-203.

doi:10.1055/s-2006-924290

Heffernan, K. S., Jae, S. Y., Echols, G. H., Lepine, N. R., & Fernhall, B. (2007). Arterial

stiffness and wave reflection following exercise in resistance-trained men.

Medicine and Science in Sports and Exercise, 39(5), 842-848.

doi:10.1249/mss.0b013e318031b03c

Heffernan, K. S., Jae, S. Y., Edwards, D. G., Kelly, E. E., & Fernhall, B. (2007). Arterial

stiffness following repeated Valsalva maneuvers and resistance exercise in young

126

men. Applied Physiology, Nutrition, and Metabolism, 32(2), 257-264.

doi:10.1139/h06-107

Heffernan, K. S., Kelly, E. E., Collier, S. R., & Fernhall, B. (2006). Cardiac autonomic

modulation during recovery from acute endurance versus resistance exercise.

European Journal of Cardiovascular Prevention and Rehabilitation, 13(1), 80-86.

Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16449868

Heffernan, K. S., Rossow, L., Jae, S. Y., Shokunbi, H. G., Gibson, E. M., & Fernhall, B.

(2006). Effect of single-leg resistance exercise on regional arterial stiffness.

European Journal of Applied Physiology, 98(2), 185-190. doi:10.1007/s00421-

006-0259-9

Heffernan, K. S., Sosnoff, J. J., Jae, S. Y., Gates, G. J., & Fernhall, B. (2008). Acute

resistance exercise reduces heart rate complexity and increases QTc interval.

International Journal of Sports Medicine, 29(4), 289-293. doi:10.1055/s-2007-

965363

Holm, S. (1979). A simple sequentially rejective multiple test procedure. Scandinavian

Journal of Statistics, 6(2), 65-70. Retrieved from www.jstor.org/stable/4615733

Jackson, A. S., & Pollock, M. L. (1978). Generalized equations for predicting body

density of men. British Journal of Nutrition, 40(3), 497-504. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/718832

127

Jackson, A. S., Pollock, M. L., & Ward, A. (1980). Generalized equations for predicting

body density of women. Medicine and Science in Sports and Exercise, 12(3), 175-

181. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/7402053

Jensen, M. P., Chen, C., & Brugger, A. M. (2003). Interpretation of visual analog scale

ratings and change scores: a reanalysis of two clinical trials of postoperative pain.

Journal of Pain, 4(7), 407-414. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/14622683

Jensen-Urstad, M., & Ahlborg, G. (1992). Is the high lactate release during arm exercise

due to a low training status? Clinical Physiology, 12(4), 487-496.

doi:doi:10.1111/j.1475-097X.1992.tb00352.x

Jouven, X., Empana, J.-P., Schwartz, P. J., Desnos, M., Courbon, D., & Ducimetière, P.

(2005). Heart-rate profile during exercise as a predictor of sudden death. New

England Journal of Medicine, 352(19), 1951-1958.

Julius, S., Palatini, P., Kjeldsen, S. E., Zanchetti, A., Weber, M. A., McInnes, G. T., . . .

Koylan, N. (2012). Usefulness of heart rate to predict cardiac events in treated

patients with high-risk systemic hypertension. American Journal of Cardiology,

109(5), 685-692. doi:10.1016/j.amjcard.2011.10.025

Kang, J., Chaloupka, E. C., Mastrangelo, M. A., & Angelucci, J. (1999). Physiological

responses to upper body exercise on an arm and a modified leg ergometer.

Medicine and Science in Sports and Exercise, 31(10), 1453-1459. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/10527319

128

Kannankeril, P. J., Le, F. K., Kadish, A. H., & Goldberger, J. J. (2004). Parasympathetic

effects on heart rate recovery after exercise. Journal of Investigative Medicine,

52(6), 394-401. doi:10.1136/jim-52-06-34

Kannel, W. B., Gordon, T., & Schwartz, M. J. (1971). Systolic versus diastolic blood

pressure and risk of coronary heart disease. The Framingham study. American

Journal of Cardiology 27(4), 335-346. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/5572576

Kingsley, J. D., Hochgesang, S., Brewer, A., Buxton, E., Martinson, M., & Heidner, G.

(2014). Autonomic modulation in resistance-trained individuals after acute

resistance exercise. International Journal of Sports Medicine, 35(10), 851-856.

doi:10.1055/s-0034-1371836

Kingsley, J. D., Mayo, X., Tai, Y. L., & Fennell, C. (2016). Arterial stiffness and

autonomic modulation after free-weight resistance exercises in resistance trained

individuals. Journal of Strength and Conditioning Research, 30(12), 3373-3380.

doi:10.1519/JSC.0000000000001461

Kingsley, J. D., Tai, Y. L., Marshall, E. M., Glasgow, A., Oliveira, R., Parks, J. C., &

Mayo, X. (2018). Autonomic modulation and baroreflex sensitivity after acute

resistance exercise: responses between sexes. The Journal of Sports Medicine and

Physical Fitness. doi:10.23736/S0022-4707.18.08864-3

Kingsley, J. D., Tai, Y. L., Mayo, X., Glasgow, A., & Marshall, E. (2017). Free-weight

resistance exercise on pulse wave reflection and arterial stiffness between sexes in

129

young, resistance-trained adults. European Journal of Sports Science, 17(8),

1056-1064. doi:10.1080/17461391.2017.1342275

Kingwell, B. A., Berry, K. L., Cameron, J. D., Jennings, G. L., & Dart, A. M. (1997).

Arterial compliance increases after moderate-intensity cycling. American Journal

of Physiology, 273(5 Pt 2), H2186-2191. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/9374752

Kraemer, W. J., & Ratamess, N. A. (2004). Fundamentals of resistance training:

progression and exercise prescription. Medicine and Science in Sports and

Exercise, 36(4), 674-688. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/15064596

Kuusela, T. A., Jartti, T. T., Tahvanainen, K. U., & Kaila, T. J. (2002). Nonlinear

methods of biosignal analysis in assessing terbutaline-induced heart rate and

blood pressure changes. American Journal of Physiology: Heart and Circulatory

Physiology, 282(2), H773-783. doi:10.1152/ajpheart.00559.2001

La Rovere, M. T., Pinna, G. D., Hohnloser, S. H., Marcus, F. I., Mortara, A., Nohara, R.,

. . . Schwartz, P. J. (2001). Baroreflex sensitivity and heart rate variability in the

identification of patients at risk for life-threatening arrhythmias: implications for

clinical trials. Circulation, 103(16), 2072-2077. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/11319197

Laurent, S., Boutouyrie, P., Asmar, R., Gautier, I., Laloux, B., Guize, L., . . . Benetos, A.

(2001). Aortic stiffness is an independent predictor of all-cause and

130

cardiovascular mortality in hypertensive patients. Hypertension, 37(5)(1524-4563

(Electronic)), 1236-1241.

Lemos, S., Figueiredo, T., Marques, S., Leite, T., Cardozo, D., Willardson, J. M., &

Simao, R. (2018). Effects of strength training sessions performed with different

exercise orders and intervals on blood pressure and heart rate variability. Int J

Exerc Sci, 11(2), 55-67. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/29795724

Likert, R. (1932). A technique for the measurement of attitudes. Archives of Psychology,

22 140, 55-55.

Lithander, F. E., Herlihy, L. K., Walsh, D. M., Burke, E., Crowley, V., & Mahmud, A.

(2013). Postprandial effect of dietary fat quantity and quality on arterial stiffness

and wave reflection: a randomised controlled trial. Nutrition Journal, 12, 93.

doi:10.1186/1475-2891-12-93

London, G. M., & Cohn, J. N. (2002). Prognostic application of arterial stiffness: task

forces. American Journal of Hypertension, 15(8), 754-758. doi:10.1016/s0895-

7061(02)02966-7

Machado-Vidotti, H. G., Mendes, R. G., Simoes, R. P., Castello-Simoes, V., Catai, A.

M., & Borghi-Silva, A. (2014). Cardiac autonomic responses during upper versus

lower limb resistance exercise in healthy elderly men. Braz J Phys Ther, 18(1), 9-

18. doi:10.1590/s1413-35552012005000140

131

Mackenzie, I. S., Wilkinson, I. B., & Cockcroft, J. R. (2002). Assessment of arterial

stiffness in clinical practice. Quarterly Journal of Medicine: Monthly Journal of

the Association of Physicians., 95(2), 67-74. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/11861952

Mayo, X., Iglesias-Soler, E., Carballeira-Fernandez, E., & Fernandez-Del-Olmo, M.

(2016). A shorter set reduces the loss of cardiac autonomic and baroreflex control

after resistance exercise. European Journal of Sports Science, 16(8), 996-1004.

doi:10.1080/17461391.2015.1108367

McEniery, C. M., Cockcroft, J. R., Roman, M. J., Franklin, S. S., & Wilkinson, I. B.

(2014). Central blood pressure: current evidence and clinical importance.

European Heart Journal, 35(26), 1719-1725. doi:10.1093/eurheartj/eht565

Mendonca, G. V., Heffernan, K. S., Rossow, L., Guerra, M., Pereira, F. D., & Fernhall,

B. (2010). Sex differences in linear and nonlinear heart rate variability during

early recovery from supramaximal exercise. Applied Physiology, Nutrition, and

Metabolism. Physiologie Appliquée, Nutrition et Métabolisme, 35(4), 439-446.

doi:10.1139/H10-028

Michas, F., Manios, E., Stamatelopoulos, K., Koroboki, E., Toumanidis, S., Panerai, R.

B., & Zakopoulos, N. (2012). Baroreceptor reflex sensitivity is associated with

arterial stiffness in a population of normotensive and hypertensive patients. Blood

Pressure Monitoring, 17(4), 155-159. doi:10.1097/MBP.0b013e32835681fb

132

Mitchell, J. H. (2012). Neural control of the circulation during exercise: insights from the

1970-1971 Oxford studies. Experimental Physiology, 97(1), 14-19.

doi:10.1113/expphysiol.2011.058156

Moreira, O. C., Faraci, L. L., de Matos, D. G., Mazini Filho, M. L., da Silva, S. F., Aidar,

F. J., . . . de Oliveira, C. E. (2017). ardiovascular responses to unilateral, bilateral,

and alternating limb resistance exercise performed using different body segments.

Journal of Strength and Conditioning Research, 31(3), 644-652.

doi:10.1519/JSC.0000000000001160

Moreno, I. L., Pastre, C. M., Ferreira, C., de Abreu, L. C., Valenti, V. E., & Vanderlei, L.

C. (2013). Effects of an isotonic beverage on autonomic regulation during and

after exercise. Journal of the International Society of Sports Nutrition, 10(1), 2.

doi:10.1186/1550-2783-10-2

Nichols, W. W. (2005). Clinical measurement of arterial stiffness obtained from

noninvasive pressure waveforms. American Journal of Hypertension, 18(1 Pt 2),

3S-10S. doi:10.1016/j.amjhyper.2004.10.009

O'Rourke, M. F., Adji, A., Namasivayam, M., & Mok, J. (2011). Arterial aging: a review

of the pathophysiology and potential for pharmacological intervention. Drugs and

Aging, 28(10), 779-795. doi:10.2165/11592730-000000000-00000

O'Rourke, M. F., & Nichols, W. W. (2003). Use of arterial transfer function for the

derivation of aortic waveform characteristics. Journal of Hypertension, 21(11),

2195-2197. Retrieved from

133

https://journals.lww.com/jhypertension/Fulltext/2003/11000/Use_of_arterial_tran

sfer_function_for_the.32.aspx

O'Rourke, M. F., & Nichols, W. W. (2005). Aortic diameter, aortic stiffness, and wave

reflection increase with age and isolated systolic hypertension. Hypertension,

45(4), 652-658. doi:10.1161/01.HYP.0000153793.84859.b8

O’Rourke, M. F., & Pauca, A. L. (2004). Augmentation of the aortic and central arterial

pressure waveform. Blood Pressure Monitoring, 9(4), 179-185. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/15311144

Okamoto, T., Masuhara, M., & Ikuta, K. (2009). Upper but not lower limb resistance

training increases arterial stiffness in humans. European Journal of Applied

Physiology 107(2), 127-134. doi:10.1007/s00421-009-1110-x

Okuno, N. M., Pedro, R. E., Leicht, A. S., de Paula Ramos, S., & Nakamura, F. Y.

(2014). Cardiac autonomic recovery after a single session of resistance exercise

with and without vascular occlusion. Journal of Strength and Conditioning

Research, 28(4), 1143-1150. doi:10.1519/JSC.0000000000000245

Pagani, M., Lombardi, F., Guzzetti, S., Sandrone, G., Rimoldi, O., Malfatto, G., . . .

Malliani, A. (1984). Power spectral density of heart rate variability as an index of

sympatho-vagal interaction in normal and hypertensive subjects. Journal of

Hypertension, 2(3), S383-385. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/6599685

134

Parati, G., & Bilo, G. (2012). Arterial baroreflex modulation of sympathetic activity and

arterial wall properties: new evidence. Hypertension, 59(1), 5-7.

doi:10.1161/hypertensionaha.111.182766

Parati, G., Di Rienzo, M., Bertinieri, G., Pomidossi, G., Casadei, R., Groppelli, A., . . .

Mancia, G. (1988). Evaluation of the baroreceptor-heart rate reflex by 24-hour

intra-arterial blood pressure monitoring in humans. Hypertension, 12(2), 214-222.

Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/3410530

Parati, G., Di Rienzo, M., & Mancia, G. (2000). How to measure baroreflex sensitivity:

from the cardiovascular laboratory to daily life. Journal of Hypertension, 18(1), 7-

19. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/10678538

Pauca, A. L., O'Rourke, M. F., & Kon, N. D. (2001). Prospective evaluation of a method

for estimating ascending aortic pressure from the radial artery pressure waveform.

Hypertension, 38(4), 932-937. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/11641312

Polito, M. D., & Farinatti, P. T. (2009). The effects of muscle mass and number of sets

during resistance exercise on postexercise hypotension. Journal of Strength and

Conditioning Research, 23(8), 2351-2357. doi:10.1519/JSC.0b013e3181bb71aa

Pollock, M. L., Franklin, B. A., Balady, G. J., Chaitman, B. L., Fleg, J. L., Fletcher, B., . .

. Bazzarre, T. (2000). AHA Science Advisory. Resistance exercise in individuals

with and without cardiovascular disease: benefits, rationale, safety, and

prescription: An advisory from the Committee on Exercise, Rehabilitation, and

135

Prevention, Council on Clinical Cardiology, American Heart Association;

Position paper endorsed by the American College of Sports Medicine.

Circulation, 101(7), 828-833. doi:10.1161/01.cir.101.7.828

Pratley, R., Nicklas, B., Rubin, M., Miller, J., Smith, A., Smith, M., . . . Goldberg, A.

(1994). Strength training increases resting metabolic rate and norepinephrine

levels in healthy 50- to 65-yr-old men. Journal of Applied Physiology, 76(1), 133-

137. doi:10.1152/jappl.1994.76.1.133

Raven, P. B., Fadel, P. J., & Smith, S. A. (2002). The influence of central command on

baroreflex resetting during exercise. Exercise and Sport Sciences Reviews, 30(1),

39-44. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11800498

Rezk, C. C., Marrache, R. C., Tinucci, T., Mion, D., Jr., & Forjaz, C. L. (2006). Post-

resistance exercise hypotension, hemodynamics, and heart rate variability:

influence of exercise intensity. European Journal of Applied Physiology, 98(1),

105-112. doi:10.1007/s00421-006-0257-y

Richman, J. S., & Moorman, J. R. (2000). Physiological time-series analysis using

approximate entropy and sample entropy. American Journal of Physiology: Heart

and Circulatory Physiology, 278(6), H2039-2049.

doi:10.1152/ajpheart.2000.278.6.H2039

Safar, M. E., Blacher, J., Mourad, J. J., & London, G. M. (2000). Stiffness of carotid

artery wall material and blood pressure in humans: application to antihypertensive

136

therapy and stroke prevention. Stroke, 31(3), 782-790.

doi:10.1161/01.str.31.3.782

Sawka, M. N. (1986). Physiology of upper body exercise. Exercise and Sport Sciences

Reviews, 14, 175-211. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/3525185

Sawka, M. N., Foley, M. E., Pimental, N. A., Toner, M. M., & Pandolf, K. B. (1983).

Determination of maximal aerobic power during upper-body exercise. Journal of

Applied Physiology: Respiratory, Environmental and Exercise Physiology, 54(1),

113-117. doi:10.1152/jappl.1983.54.1.113

Seals, D. R. (1993). Influence of active muscle size on sympathetic nerve discharge

during isometric contractions in humans. Journal of Applied Physiology, 75(3),

1426-1431. doi:10.1152/jappl.1993.75.3.1426

Simao, R., Fleck, S. J., Polito, M., Monteiro, W., & Farinatti, P. (2005). Effects of

resistance training intensity, volume, and session format on the postexercise

hypotensive response. Journal of Strength and Conditioning Research, 19(4),

853-858. doi:10.1519/R-16494.1

Smith, L. L., Kukielka, M., & Billman, G. E. (2005). Heart rate recovery after exercise: a

predictor of ventricular fibrillation susceptibility after myocardial infarction.

American Journal of Physiology: Heart and Circulatory Physiology, 288(4),

H1763-1769. doi:10.1152/ajpheart.00785.2004

137

Stergiopulos, N., & Westerhof, N. (1998). Determinants of pulse pressure. Hypertension,

32(3), 556-559. doi:10.1161/01.hyp.32.3.556

Sugawara, J., Tanabe, T., Miyachi, M., Yamamoto, K., Takahashi, K., Iemitsu, M., . . .

Matsuda, M. (2003). Non-invasive assessment of cardiac output during exercise

in healthy young humans: comparison between Modelflow method and Doppler

echocardiography method. Acta Physiologica Scandinavica, 179(4), 361-366.

doi:10.1046/j.0001-6772.2003.01211.x

Swierblewska, E., Hering, D., Kara, T., Kunicka, K., Kruszewski, P., Bieniaszewski, L., .

. . Narkiewicz, K. (2010). An independent relationship between muscle

sympathetic nerve activity and pulse wave velocity in normal humans. Journal of

Hypertension, 28(5), 979-984.

Tai, Y. L., Gerhart, H., Mayo, X., & Kingsley, J. D. (2018). Acute resistance exercise

using free weights on aortic wave reflection characteristics. Clinical Physiology

and Functional Imaging, 38(1), 145-150. doi:10.1111/cpf.12396

Tai, Y. L., Marshall, E. M., Glasgow, A., Parks, J. C., Sensibello, L., & Kingsley, J. D.

(2018). Pulse wave reflection responses to bench press with and without practical

blood flow restriction. Applied Physiology, Nutrition, and Metabolism, 1-7.

doi:10.1139/apnm-2018-0265

Tai, Y. L., Marshall, E. M., Glasgow, A., Parks, J. C., Sensibello, L., & Kingsley, J. D.

(2019). Autonomic modulation following an acute bout of bench press with and

138

without blood flow restriction. European Journal of Applied Physiology, 119(10),

2177-2183. doi:10.1007/s00421-019-04201-x

Takazawa, K., O'Rourke, M. F., Fujita, M., Tanaka, N., Takeda, K., Kurosu, F., &

Ibukiyama, C. (1996). Estimation of ascending aortic pressure from radial arterial

pressure using a generalised transfer function. Zeitschrift für Kardiologie, 85

Suppl 3, 137-139. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/8896320

Task Force of the European Society of Cardiology and the North American Society of

Pacing and Electrophysiology. (1996). Heart rate variability: Standards of

measurement, physiological interpretation, and clinical use. European Heart

Journal, 17(3), 354-381. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/8737210

Townsend, R. R., Wilkinson, I. B., Schiffrin, E. L., Avolio, A. P., Chirinos, J. A.,

Cockcroft, J. R., . . . American Heart Association Council on, H. (2015).

Recommendations for improving and standardizing vascular research on arterial

stiffness: a scientific statement from the American Heart Association.

Hypertension, 66(3), 698-722. doi:10.1161

Tulppo, M. P., Makikallio, T. H., Takala, T. E., Seppanen, T., & Huikuri, H. V. (1996).

Quantitative beat-to-beat analysis of heart rate dynamics during exercise.

American Journal of Physiology, 271(1 Pt 2), H244-252.

doi:10.1152/ajpheart.1996.271.1.H244

139

van Rooijen, M., Hansson, L. O., Frostegard, J., Silveira, A., Hamsten, A., & Bremme, K.

(2006). Treatment with combined oral contraceptives induces a rise in serum C-

reactive protein in the absence of a general inflammatory response. Journal of

Thrombosis and Haemostasis, 4(1), 77-82. doi:10.1111/j.1538-

7836.2005.01690.x

Victor, R. G., Bertocci, L. A., Pryor, S. L., & Nunnally, R. L. (1988). Sympathetic nerve

discharge is coupled to muscle cell pH during exercise in humans. Journal of

Clinical Investigation, 82(4), 1301-1305. doi:10.1172/JCI113730

Volianitis, S., Yoshiga, C. C., Nissen, P., & Secher, N. H. (2004). Effect of fitness on arm

vascular and metabolic responses to upper body exercise. American Journal of

Physiology: Heart and Circulatory Physiology, 286(5), H1736-1741.

doi:10.1152/ajpheart.01001.2003

Weber, T., Auer, J., O'Rourke, M. F., Kvas, E., Lassnig, E., Berent, R., & Eber, B.

(2004). Arterial stiffness, wave reflections, and the risk of coronary artery disease.

Circulation, 109(2), 184-189. doi:10.1161/01.CIR.0000105767.94169.E3

Weber, T., O'Rourke, M. F., Lassnig, E., Porodko, M., Ammer, M., Rammer, M., &

Eber, B. (2010). Pulse waveform characteristics predict cardiovascular events and

mortality in patients undergoing coronary angiography. Journal of Hypertension,

28(4), 797-805. doi:10.1097/HJH.0b013e328336c8e9

140

Wesseling, K. H., Jansen, J. R., Settels, J. J., & Schreuder, J. J. (1993). Computation of

aortic flow from pressure in humans using a nonlinear, three-element model. J

Appl Physiol (1985), 74(5), 2566-2573. doi:10.1152/jappl.1993.74.5.2566

Westcott, W. L. (2012). Resistance training is medicine: effects of strength training on

health. Current Sports Medicine Reports, 11(4), 209-216.

doi:10.1249/JSR.0b013e31825dabb8

White, W. B. (1999). Heart rate and the rate-pressure product as determinants of

cardiovascular risk in patients with hypertension. American Journal of

Hypertension, 12(2 Pt 2), 50S-55S. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/10090295

Wilkinson, I. B., MacCallum, H., Flint, L., Cockcroft, J. R., Newby, D. E., & Webb, D. J.

(2000). The influence of heart rate on augmentation index and central arterial

pressure in humans. Journal of Physiology, 525 Pt 1, 263-270. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/10811742

Wirtz, N., Wahl, P., Kleinoder, H., & Mester, J. (2014). Lactate kinetics during multiple

set resistance exercise. Journal of Sports Science & Medicine, 13(1), 73-77.

Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24570608

Wolinsky, H., & Glagov, S. (1964). Structural basis for the static mechanical properties

of the aortic media. Circulation Research, 14, 400-413. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/14156860

141

Yoon, E. S., Jung, S. J., Cheun, S. K., Oh, Y. S., Kim, S. H., & Jae, S. Y. (2010). Effects

of acute resistance exercise on arterial stiffness in young men. Korean Circulation

Journal, 40(1), 16-22. doi:10.4070/kcj.2010.40.1.16