Ischemic Preconditioning and Exercise Performance: Shedding Light Through Smallest Worthwhile Change

European Journal of Applied Physiology (2019) 119:2123–2149 https://doi.org/10.1007/s00421-019-04214-6

INVITED REVIEW

Ischemic preconditioning and exercise performance: shedding light through smallest worthwhile change

Moacir Marocolo1 · Mario A. Moura Simim2 · Anderson Bernardino1 · Iury Reis Monteiro1 · Stephen D. Patterson3 · Gustavo R. da Mota4

Received: 14 March 2019 / Accepted: 19 August 2019 / Published online: 26 August 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019

Abstract Ischemic preconditioning (IPC) has been suggested as a potential ergogenic aid to improve exercise performance, although controversial fndings exist. The controversies may be explained by several factors, including the mode of exercise, the ratio between the magnitude of improvement, or the error of measurement and physiological meaning. However, a relevant aspect has been lacking in the literature: the interpretation of the fndings considering statistical tests and adequate efect size (ES) according to the ftness level of individuals. Thus, we performed a systematic review with meta-analysis to update the efects of IPC on exercise performance and physiological responses, using traditional statistics (P values), ES, and smallest worth change (SWC) approach contextualizing the IPC application to applied Sports and Exercise performance. Forty-fve studies met the inclusion criteria. Overall, the results show that IPC has a minimal or nonsignifcant efect on performance considering the ftness level of the individuals, using statistical approaches (i.e., tests with P value, ES, and SWC). Therefore, IPC procedures should be revised and refned in future studies to evaluate if IPC promotes positive efects on performance in a real-world scenario with more consistent interpretation.

Keywords Ischemia · Sports · Skeletal muscle · Statistical · Blood fow occlusion · Ergogenic

Abbreviations SWC Smallest worthwhile change CI Confdence interval VO2max Maximal oxygen consumption ES Efect size I2 Heterogeneity statistic IPC Ischemic preconditioning Introduction PRISMA Preferred reporting items for systematic reviews and meta-analysis Ischemic preconditioning (IPC) is a non-invasive technique Q Cochran test conducting transient peripheral hypoxia and subsequently RPE Rating of perceived exertion enhance tissue tolerance against ischemia–reperfusion injury (Paradis-Deschenes et al. 2016b). This technique promoted greater protection of heart tissue against infarct size (Murry et al. 1986), and has become widespread. Communicated by Michael Lindinger. Following numerous studies demonstrating tissue protec- * Moacir Marocolo tion in clinical experiments (Eisen et al. 2004), the IPC [email protected] technique has been suggested as a potential ergogenic aid to improve exercise performance (Marocolo et al. 2016a, 1 Department of Physiology, Federal University of Juiz de 2017b; Incognito et al. 2016), focussing mainly on swim- Fora, Juiz de Fora, Minas Gerais, Brazil ming (Marocolo et al. 2015), cycling (Crisafulli et al. 2 Institute of Physical Education and Sports, Federal University 2011b), and running performance (Bailey et al. 2012b). of Ceará, Fortaleza, Brazil Furthermore, studies have investigated IPC on resistance 3 Faculty of Sport, Health, and Applied Science, St. Mary’s (Barbosa et al. 2015; Cochrane et al. 2013; Marocolo et al. University, Twickenham, London, UK 2016a), intermittent (Marocolo et al. 2017a), and fatiguing 4 Department of Sport Sciences, Federal University isometric (Tanaka et al. 2016) exercises. Despite numerous of Triangulo Mineiro, Uberaba, Brazil

Vol.:(0123456789)1 3 2124 European Journal of Applied Physiology (2019) 119:2123–2149 investigations, the results are inconsistent, and an “ideal” IPC protocol has not yet been standardised (Marocolo et al. 2016a, 2017b, 2018; da Mota and Marocolo 2016; Incognito et al. 2016), making it difcult to elucidate the physiological mechanisms behind IPC. A few proposed mechanisms have been considered, frst, the hyperemia experienced following the occlusion phase may play a role due to nitric oxide production (Singh et al. 2017). Further- more, an increased phosphocreatine resynthesis, altered oxy-deoxyhaemoglobin kinetics (Bailey et al. 2012a), and increased oxygen consumption (Andreas et al. 2011) may play a role in improving exercise performance. Investigation of the IPC effects on exercise performance should consider the analysis of a number of set parameters, including statistical tests, the ratio between Fig. 1 the magnitude of the improvement, and the error of meas- Smallest worthwhile changes recommendation urement. In addition, there should be consideration of the physiological meaning and the context of the ftness level and/or mode of exercise, and adequate efect size (ES) statistics (P values), ES and SWC approach contextualizing interpretations. For instance, improvements with small ES the IPC application for performance. could be important when evaluating elite, but not amateur athletes (Marocolo et al. 2018). In sports sciences/medicine research, the P values from traditional statistics have Methods been criticized (Buchheit 2016b, 2017). When P values are considered in isolation from other statistical indicators Literature search (e.g., confdence interval and ES), it may produce misleading conclusions, including misleading practical applica- The Preferred Reporting Items for Systematic Reviews and tions, wasted resources, and time. For example, one study Meta-analysis (PRISMA) recommendations were followed may show a signifcant diference (P < 0.05) after an inter- (Moher et al. 2009). This study identifed IPC and exercise vention, but with small ES in amateur athletes which has studies located primarily through the PubMed database limited beneft when practically applied (Buchheit 2016b; with second-order internet search engines including Google Marocolo et al. 2018). Furthermore, the lack of magnitude Scholar (using [advanced search], [all felds]), and other of efects, which matters in the most cases (Cohen 1994), online journals. The following crucial terms (1) “ischemic are motivating sports scientists to look for more realis- preconditioning”; (2) “blood fow” and “hyperemia”; and (3) tic approaches instead of only P value analysis. In this “blood fow occlusion” were combined with “exercise per- context, the smallest worthwhile change (SWC) has been formance”, “athletes”, “exercise”, and “performance”. Stud- highly suggested for the analysis of exercise performance ies selected were limited to those written in the English lan- studies (Buchheit 2016a) due to its singular specifcity for guage (Morrison et al. 2012; Juni et al. 2002) and included sports sciences area (e.g., small sample size, the practical journal articles, ahead of print articles, and a master thesis. relevance of the changes, and the typical error of meas- urements) (Marocolo et al. 2017b; Haugen and Buchheit Selection criteria 2016; Hopkins et al. 2009). In this context, the SWC calculated by 0.2 multiplied by standard deviation (SD) is more Studies were included based on strict criteria determined relevant for high ftness level participants, while the SWC by 2 investigators including: (1) original study; (2) IPC calculated by 0.6 multiplied by SD is relevant for both performed prior to the exercise; (3) evaluation of healthy high and low ftness level participants (Fig. 1). participants; (4) conduction of exercise or efort test; and Although IPC is an exciting tool to be used as an ergo- (5) analysis of performance. Systematic review articles, genic aid to enhance performance, no research has deter- meta-analyses, and studies with only animals or non-healthy mined the IPC efects considering the SWC approach in participants were excluded from this review. The literature combination with the traditional statistical analyses, which search included papers from 1st January 1900 to 23rd May could be relevant. Thus, this systematic review and meta- 2018. The selected studies were read rigorously to deter- analysis aimed to update the IPC efects on exercise per- mine if they met the inclusion/exclusion criteria. The search, formance and physiological indicators using traditional selection, and inclusion process can be seen in Fig. 2. The

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Fig. 2 Flow chart of search database

search displayed a total of 3466 papers, which were reduced possible score = 15 points. In most questions, the expres- to 1779 after exclusion of duplicate publications. Out of sion “clearly” refers to the fact that information is explic- these papers, we excluded another 1205 by title, leaving itly presented in the paper. The general quality of each 574 yet to be selected. Finally, after checking those papers publication was achieved using the sum of the 15 criteria for our defned inclusion criteria, 45 remained for further scores. After this initial screening, another author checked analysis. all selected papers according to the quality criteria and arrived at the conclusion, in concordance with the other Quality assessment and data extraction author that the 17 candidate papers should be included in the meta-analysis. The quality of all included papers was estimated accord- The variables were divided into categories, e.g., perfor- ing to a checklist based on and adapted from the studies mance or physiological variables associated with perfor- by Downs and Black (1998) and van Velzen et al. (2006). mance and modalities, e.g., swimming, cycling, running, At frst, only one investigator analysed the methodologi- and resistance exercises. This classifcation aimed at a cal quality of the articles. There were 3 possible scores better description of the results, and most of the studies (Yes = 1 point, Unclear = 1/2 point, No = 0 points) for evaluated more than one variable. each item in the checklist (Table 1) with the maximum

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Table 1 Quality criteria used to analyze the publications 0 ½ 1

Reporting 1. Is the hypothesis/aim/objective of the study clearly described? No Unclear Yes 2. Are the main outcomes to be measured clearly described in the Introduction? No Unclear Yes 3. Are the characteristics of the subjects included in the study clearly described? No Unclear Yes 4. Are the interventions of interest clearly described? No Unclear Yes 5. Are the main fndings of the study clearly described? No Unclear Yes 6. Does the study provide estimates of the random variability in the data for the main outcomes? No Unclear Yes 7. Were the instruments of testing reliable? No Unclear Yes 8. Was a follow-up duration sufciently described and consistent within the study? No Unclear Yes 9. Number of participants included in study fndings < 5 6–15 > 16 Analysis and presentation 10. Have actual probability values been reported (e.g. 0.035 rather than < 0.05) for the main outcomes No Unclear Yes except, where the probability value is less than 0.001? 11. Was there a statement adequately describing or referencing all statistical procedures used? No Unclear Yes 12. Were the statistical analyses used appropriate? No Unclear Yes 13. Was the presentation of results satisfactory? No Unclear Yes 14. Were confdence intervals given for the main results? No Unclear Yes 15. Was the conclusion drawn from the statistical analysis justifed? No Unclear Yes

Data analysis and physiological variables of the studies. The magnitude of the ES was classified as trivial (< 0.2), small The meta-analysis was performed separately for physiologi- (> 0.2–0.6), moderate (> 0.6–1.2), large (> 1.2–2.0) and cal and performance variables. No authors were asked to very large (> 2.0–4.0) based on the guidelines from Bat- send the paper data and all calculations were performed with terham and Hopkins (Batterham and Hopkins 2006). In only the data presented in each study. The weight of the stud- addition, the SWC was estimated for all variables, whose ies was calculated, confdence interval (95% CI) and stand- studies provided enough data for this. SWC was consid- ardized mean diference for each study individually; these ered as the standard deviation multiplied by 0.2 or 0.6, values were then combined for the analysis of the studies. based on Cohen’s ES principle (Buchheit 2016b; Buch- The analysis was performed with a random-efects model heit et al. 2014). The significance level was 0.05, and (Borenstein et al. 2009; Pigott 2012), and heterogeneity was GraphPad ® (Prism 6.0, San Diego, CA, USA) was used assessed by the Q Cochran test (Cochran 1954), which was for the analysis. completed with I2 (Higgins and Thompson 2002). The sample was homogeneous (P ≥ 0.05) for the Q test and I2 value (≤ 25%). The general purpose of the analysis was tested Results using the Z test (Zaykin 2011). The criterion for statistical signifcance was P < 0.05 for 95% CI. These analyses were Overall, the data suggest that a high-quality of studies have performed using the Review Manager Software (version 5.3, been selected. The efects of IPC on exercise performance, Copenhagen: The Nordic Cochrane Centre, The Cochrane according to either traditional (P values) or alternative Collaboration 2014). (SWC, ES) statistical tools, present a low magnitude. In The Shapiro–Wilk test was applied to verify the normal addition, almost all studies lack real-world context (e.g., distribution of the data. The Spearman test was used to feld tests or evaluations during competitions). examine the correlation between the percentage changes in the performance and physiological variables that Quality of the papers showed statistical significance with “duration of exercise” (extracted from the information provided in each The quality scores of the analysed studies are shown in study), “total time of IPC maneuver”, and “time prior to Table 2. All of the studies achieved the required stand- exercise”. The ES was calculated to determine the mean- ard to be considered a low risk of bias (mean quality ingfulness of the difference (Cohen 1988) in performance score = 12.2 ± 1.4; 81%). Table 3 summarizes the characteristics of the studies examining IPC while, in the Table 4,

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Table 2 Scores assigned to each of the studies (in chronological order) for each of the quality (Q) criteria References Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10 Q11 Q12 Q13 Q14 Q15 Score (% of max) de Groot et al. (2010) 1 0.5 1 1 1 1 1 0.5 0.5 1 1 1 1 0 1 12.5 (83) Barr (2011) 1 1 1 1 1 1 1 1 0.5 1 1 1 1 0 1 13.5 (90) Crisafulli et al. (2011) 1 1 1 1 1 1 1 1 0.5 0 1 1 1 0 1 12.5 (83) Foster et al. (2011) 1 1 1 1 1 1 1 1 1 1 1 1 1 0 1 14.0 (93) Jean-St-Michel et al. (2011) 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 15.0 (100) Bailey et al. (2012b) 1 0.5 1 1 1 1 1 0.5 1 1 1 1 1 1 1 14.0 (93) Beaven et al. (2012) 1 0.5 1 1 1 0.5 1 1 0.5 0 1 0.5 1 1 1 12.0 (80) Clevidence et al. (2012) 1 1 1 1 1 1 1 0.5 0.5 0 1 1 1 0 1 12.0 (80) Cochrane et al. (2013) 1 1 1 1 1 1 1 1 0.5 1 1 1 1 0 1 13.5 (90 Gibson et al. (2013) 1 1 1 1 1 1 1 1 0.5 0 1 1 0.5 0 1 12.0 (80) Foster et al. (2011) 1 1 1 1 1 1 1 0.5 1 1 1 1 1 0 1 13.5 (90) Kjeld et al. (2014) 0.5 1 1 1 1 1 1 0.5 1 0 1 1 1 0 1 12.0 (80) Paixao et al. (2014) 1 1 1 1 1 1 1 0.5 1 0 1 1 0.5 0 1 12.0 (80) Barbosa et al. (2015) 1 1 1 1 1 1 1 0.5 0.5 1 1 1 1 0 1 13.0 (87 Cruz et al. (2015) 1 1 1 1 1 1 1 1 0.5 1 1 1 1 0 1 13.5 (90) Gibson et al. (2015) 1 1 1 1 1 1 1 0.5 0.5 0 1 1 1 0 1 12.0 (80) Hittinger et al. (2015) 1 1 1 1 1 1 1 0.5 1 1 1 1 1 0 1 13.5 (90) Lalonde and Curnier (2015) 1 1 1 1 1 0 1 0.5 1 1 1 1 1 0 1 12.5 (83) Marocolo et al. (2015) 1 1 1 1 1 1 1 0.5 0.5 1 1 1 1 0 1 13.0 (87) Martin et al. (2015) 1 1 1 1 1 1 1 1 0.5 1 1 1 1 1 1 14.5 (97) Patterson et al. (2015) 1 1 1 1 1 1 1 0.5 0.5 0.5 1 1 1 1 1 13.5 (90) Tocco et al. (2015) 1 1 1 1 1 1 1 1 0.5 0 1 1 1 0 1 12.5 (83) Banks et al. (2016) 1 1 1 1 1 0.5 1 0.5 0.5 0.5 1 1 1 0 1 12.0 (80) Cruz et al. (2016) 0.5 1 1 1 1 1 1 1 0.5 0.5 1 1 1 1 1 13.5 (90) Ferreira et al. (2016) 1 0.5 1 1 1 0.5 1 1 1 1 1 1 1 0 1 13.0 (87) James et al. (2016) 1 1 1 1 1 1 1 1 0.5 1 1 1 1 0 1 13.5 (90) Kaur et al. (2017) 1 1 0.5 1 1 0 1 0.5 1 1 1 1 1 0 1 12.0 (80) Marocolo et al. (2016a) 1 1 1 1 1 1 1 1 1 1 1 1 1 0 1 14.0 (93) Marocolo et al. (2016b) 1 1 1 1 1 1 1 1 0.5 1 1 1 1 0 1 13.5 (90) Northey et al. (2016) 0.5 1 1 1 1 1 1 1 1 1 1 1 1 0 1 13.5 (90) Paradis-Deschenes et al. (2016a) 1 1 1 1 1 1 1 1 0.5 0 1 1 1 0 1 12.5 (83 Tanaka et al. (2016) 1 0.5 1 1 1 0.5 1 0.5 0.5 0.5 1 1 1 0 1 11.5 (77) Sabino-Carvalho et al. (2017) 1 1 1 1 1 1 1 1 1 1 1 1 1 0 1 14.0 (93) Seeger et al. (2017) 1 1 1 1 1 1 1 1 0.5 1 1 1 1 0 1 13.5 (93) Cocking et al. (2018b) 0.5 0.5 1 1 1 1 1 0.5 1 1 1 0.5 0.5 0 0.5 11.0 (73) Grifn et al. (2018) 1 0.5 1 1 1 0.5 1 1 0.5 1 1 1 1 0 1 12.5 (83) Marocolo et al. (2017a) 1 1 1 1 1 1 1 1 0.5 1 1 1 1 0 1 13.5 (90) Page et al. (2017) 1 1 0.5 1 1 1 1 1 1 0.5 1 1 1 0 1 13.0 (87) Paradis-Deschenes et al. (2016b) 0.5 1 1 1 1 1 1 1 1 1 1 1 1 1 1 14.5 (97) Zinner et al. (2017) 1 1 0.5 1 1 1 1 0.5 0.5 1 1 1 1 1 1 13.5 (90) Cocking et al. (2018a) 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 15.0 (100) Grifn et al. (2019) 1 0.5 1 1 1 0.5 1 1 0.5 1 1 1 1 0 1 12.5 (83) Paradis-Deschenes et al. (2018) 1 1 1 1 1 0.5 1 1 0.5 1 1 1 1 1 1 14.0 (93) Richard and Billaut (2018) 0.5 0.5 1 1 1 1 0.5 1 1 1 1 1 1 1 1 13.5 (90) Williams et al. (2018) 1 1 1 1 1 1 1 0.5 1 1 1 1 1 0 1 13.5 (90)

1 3 2128 European Journal of Applied Physiology (2019) 119:2123–2149 b a HR HR 2max 2max 2max Workload trialTime Heart rate time Exhaust. Peak Ex. toler. Time trialTime SJ (w) CMJ (w) 10 m sprint 40 m sprint CK VJPP VJ Peak power Peak Mean power index Fat. Variable analyzed Variable Time trialTime Avg. Avg. Time V O Max power V O V O Time trialTime Time Time 1000 m T. Max Pw. 1 Max Pw. 1 Mean Pw. 2 Mean Pw. T. fat T. (3 × 100 rep) max mental mental break grip 100 kJ normoxia 100 kJ hypoxia jump Squat CMJ ECC exercise ECC exercise Wingate Test protocol Test 100 m time trial Incremental + 90% 10 m sprint 20 m sprint 30 m sprint - Maximal incre - Maximal incre Incremental 5 km 12.8 km Dynamic apnea apnea Static Distance time 3 Wingate/10 min 3 Wingate/10 min Rhythmic hand - Rhythmic 90 min 0–24 h 24–48–72 h 20 min Time to test to Time ~ 45 min 5 min 15 min 5 min 5 min 45 min Prior 30 min 12 min 25 min leg SAP/one 20 > SAP/one thigh 220–15/thigh 10 > pulse pressure/ 220/thigh Ischemia pressure pressure Ischemia (mmHg)/limb 15 > SAP-10/arm 220–0/thigh 220–50/thigh 50 > SAP/thigh 220/thigh 220–20/thigh ~ 200–40/thigh 40 > SAP/forearm 250–20/thigh 200–10/thigh C/IPC C/IPC C/IPC C/IPC Group P/IPC C/IPC C/P/IPC C/IPC C/IPC P/IPC P/IPC C/IPC P/IPC C/IPC ing/15 min 4 × 5 min/20 min 2 × 3 min/6 min 30 min–30 s alternat - 3 × 5 min/15 min IPC protocol IPC time Total 4 × 5 min/20 min 3 × 5 min/15 min 3 × 5 min/15 min 3 × 5 min/15 min 3 × 5 min/15 min 4 × 5 min/20 min × 5 min/20 min 5 days-4 4 × 5 min/20 min 4 × 5 min/20 min 3 × 5 min/15 min 8 14 10 24 18 20 25 17 15 13 12 15 9/13 11–6-14 N involved in involved activity physical letes Amateur cyclists Healthy and Healthy Participants Active Elite swimmers Cyclists Team sport ath - Team Healthy Healthy Healthy Running Rowers/divers Cyclists Healthy tric exercise Cycling Jump/sprints eccen - Strenuous Exercise protocol Exercise Cycling Swimming Cycling Sprint Cycling Cycling Running Healthy Rowing/apnea Cycling Handgrip Characteristics of the studies examining IPC Characteristics of theexamining studies ( 2012 ) ( 2013 ) et al. ( 2011 ) et al. ( 2012 ) ( 2013 ) ( 2011b ) ( 2010 ) ( 2012b ) ( 2014 ) ( 2015 ) Foster et al. ( 2011 ) et al. Foster et al. Beaven et al. Cochrane 3 Table References Barr ( 2011 ) Jean-St-Michel Jean-St-Michel Clevidence et al. et al. Clevidence Gibson et al. Gibson et al. Crisafulli et al. de Groot et al. et al. de Groot Bailey et al. et al. Bailey Foster et al. ( 2014 ) et al. Foster Kjeld et al. ( 2014 ) Kjeld et al. Paixao et al. et al. Paixao Barbosa et al. Barbosa et al.

1 3 European Journal of Applied Physiology (2019) 119:2123–2149 2129 ) ) ) −1 −1 −1 (l min 2 (l min 2max 2 2Peak ratio index Time to 5 km to Time m V O Blood [La] Blood [La] peak Quadriceps EMG Cardiac PCr/ATP PCr/ATP Cardiac Blood pressure PESM PCr recovery Lactate power Peak power Total Variable analyzed Variable Speed (m s Mean power output Mean power V O Ex. capacity Ex. capacity Time to exhaustion to Time V O Peak power Peak Mean power power Peak Mean power Time trialTime Heart rate [La] fatigue Overall Peak power Peak V O Bicycle level alt bic Test Prog Ramp Ramp Prog Sprint 5 × 6 s Test protocol Test 5 km Incremental Incremental/sea Incremental high Incremental Progressive Progressive 6 × 6 s Wingate 100 m time trial - Anaero Wingate 12 × 6 s sprints 24 h 5 min Time to test to Time 5 min 33 min 45 min 90 min – 15 min 5 min 30 min 10 < DAP/thigh arm 70 mmHg 200 mmHg/leg 220–50/thigh Ischemia pressure pressure Ischemia (mmHg)/limb 50 > SAP- 220/thighs (IPC) 20/thighs (C) 10–20 > SAP/thigh 220/thighs (IPC) 20/thighs (C) SAP-10/right 50 > SAP-10/right 220–5/arm 5 chambers of 5 chambers 220–20/thigh IPC C/P/IPC Group C/P/IPC C/IPC C/IPC C/IPC P/IPC C/P/IPC P/EPC P/IPC (180 min) 5 min/9 days 4 × 5 min/9 days 3 × 5 min/15 min IPC protocol IPC time Total 3 × 5 min/15 min 4 × 5 min /20 min 4 × 5 min/20 min 4 × 5 min /20 min 4 × 5 min/20 min 4 × 5 min/20 min 30 min (sic)/30 min 3 × 5 min/15 min 10 16 11 15 28 12 17 15 10 14 N adults cyclists cyclists and cyclists triathletes trained cyclists trained athletes players in sprint sports Sedentary young Trained population Trained Participants Skilled runners Recreational Recreational High trained High trained Recreationally Recreationally Healthy Recreational Recreational College hockey hockey College Recreational active active Recreational Cycling Sprint Exercise protocol Exercise Running Cycling Cycling Cycling Cycling Swimming Anaerobic cycling Anaerobic Cycling (continued) ( 2015 ) ( 2015 ) Curnier ( 2015 ) ( 2015 ) ( 2015 ) ( 2015 ) Banks et al. ( 2016 ) Banks et al. Gibson et al. Gibson et al. 3 Table References Tocco et al. ( 2015 ) et al. Tocco Cruz ( 2016 ) et al. Hittinger et al. et al. Hittinger Cruz ( 2015 ) et al. Lalonde and Marocolo et al. et al. Marocolo Martin et al. Patterson et al. et al. Patterson

1 3 2130 European Journal of Applied Physiology (2019) 119:2123–2149 (GTX2) rate 2Max 2 tions tions 2/4 mmol Status Scale Status Scale Total run time Total v V O Heart Blood [La] economy Running Caloric unit cost Variable analyzed Variable Blood [La] RPE - of repeti Number sprint time (best) Sprint time (worst) Sprint time (total) Sprint time (decr.) Blood [La] index Fatigue - of repeti Number Heart rate Speed [La]: economy Running V O Peak torque Peak Mean SJ height Mean CMJ height Recovery Perceived Soreness Perceived swimming Test squart (10 test - of 10 repeti sets tions) Incremental Test protocol Test 12-RM Test Repeated sprintRepeated 12-RM Test Graded Exercise Exercise Graded Fatiguing back back Fatiguing the test) 15 min Time to test to Time 8 min 30 min 8 min 20 min 24 h (time after 220 (IPC) 20 (P) Ischemia pressure pressure Ischemia (mmHg)/limb 220 (IPC) 20 (P) 220 (IPC) 50 (C) 10 (P) 220/20 0 mmHg 220 (IPC) 50 (C) 220 mmHg/thighs P/IPC Group P/IPC P/C/IPC C/P/IPC C/IPC C/OCC - nating thighs) 3 × 5/15 min IPC protocol IPC time Total 4 × 5 min/20 min 3 × 5 min/30 min 4 × 5 min/40 min 4 × 5 min/20 min 2 × 3 min/12 min (alter 18 21 23 13 11 12 N runners Participants Healthy Healthy Short distance swimmers college Healthy Recreational club Recreational Strength-trained - - - cise cise cise Exercise protocol Exercise Running Resistance exer Resistance Swimming Resistance exer Resistance Running Resistance exer Resistance (continued) ( 2016b ) ( 2016 ) ( 2016a ) ( 2016 ) (Post) 3 Table References ( 2017 ) Kaur et al. Marocolo et al. et al. Marocolo Ferreira et al. Marocolo et al. et al. Marocolo James et al. ( 2016 ) James et al. Northey et al. et al. Northey

1 3 European Journal of Applied Physiology (2019) 119:2123–2149 2131 consumed 2 - (incremen - (Supramaxi O 2max 2max 2 tal test) mal test) conc conc Heart (IT) rate RER (IT) Blood [La] (IT) (IT) Borg V O HR (ST) RER (ST) Blood [La] (ST) Time trialTime RPE/BORG Blood [La] trialTime 24 h Blood [La] V O Power (avg) Power Total work done work Total Blood [La] Critical power Total Heart rate RPE Blood [La] Distance Variable analyzed Variable Peak knee ext. force knee ext. Peak force knee ext. Tot. force knee ext. Avg. Muscle Hb avg. Muscle Hb peak Time to fatigue to Time Muscle oxygenation V O Ergometer Test Ergometer knee extension supramaximal 5 km Time trialTime Ramp Cycle Cycle Ramp Distance Test protocol Test Max. voluntary MVC Incremental/ 60 min 35 min 3 min 6 min Time to test to Time 18 ± 2 min 5 min 10 min 220 (IPC) 20 (P) 220 mmHg (IPC) 20 mmHg (P) 220 mmHg (IPC) 20 mmHg (P) 220 mmHg (IPC) 20 mmHg (P) Ischemia pressure pressure Ischemia (mmHg)/limb 200 (IPC) 20 (P) > 300 mmHg (IPC) cuf infation (C) No 220 (IPC) (P) ultras Therap P/IPC P/IPC P/IPC C/P/IPC Group P/IPC C/IPC C/P/IPC 4 × 5 min/20 min 4 × 5 min/20 min 4 × 5 min/40 min 4 × 5 min/20 min IPC protocol IPC time Total 3 × 5 min/15 min 3 × 5 min/15 min 4 × 5 min/20 min 12 12 12 13 10 12 18 N active males active players men Healthy Trained cyclists Trained Recreationally Recreationally Amateur soccer Participants Strength-trained Strength-trained Healthy Runners ric exercise Running Cycling Cycling YOYO intermittent YOYO Exercise protocol Exercise Isokinetic exercise Isokinetic - isomet Fatiguing Running (continued) ( 2017 ) 2017 ) ( 2018 ) ( 2017a ) et al. ( 2016a ) et al. ( 2016 ) et al. ( 2017 ) et al. Seeger et al. et al. Seeger Cocking et al. et al. Cocking Grifn et al. Marocolo et al. et al. Marocolo 3 Table References Paradis-Deschenes Paradis-Deschenes Tanaka et al. et al. Tanaka Sabino-Carvalho

1 3 2132 European Journal of Applied Physiology (2019) 119:2123–2149 ge RPE during during sprint 2 2 recovery response exchange ratio exchange SmO Peak diameter diameter Peak Blood velocity 30 s force force Peak Variable analyzed Variable Total sprint time Total Mean muscle oxy Mean blood [La] Mean MIVC CMJ DOMS CK Average force Average Δ [THb] Δ [HHb] Mean time uptake Oxygen Respiratory Ventilation Heart rate SmO 30 min (30 contract/relax cycles/min) (6 × 15 + 15 m) of 20 repetitions) voluntary knee extension 25% of MVC 25% of MVC Test protocol Test Sprint 3 × Drop-jumps (5 sets (5 sets Drop-jumps 5 sets of 5 max. 5 sets Sprint 16 × 30 m the test) 20 min Time to test to Time 15 min 24 h (time after 18.5 ± 0.1 min 45 min (IPC) (IPC) (RIPC) 220/arms (IPC) 220/legs (RIPC) 20/arms (P) Ischemia pressure pressure Ischemia (mmHg)/limb 220/arm and leg 20/thighs na leg (P) 220 mmHg (IPC) 20 mmHg (P) 200/right thigh 20/right thigh (P) 240/thighs (IPC) 180–190/arms 20/thighs (P) P/IPC Group P/IPC P/OCC P/IPC P/IPC 4 × 5 min/20 min IPC protocol IPC time Total 4 × 5 min/20 min 3 × 5 min 3 × 5 min 3 × 5 min/ 15 min 18 20 16 17 13 N trained trained active males active letes Recreationally Recreationally Participants Recreationally Recreationally Recreationally- Strength-trained Team sport ath- Team Handgrip Exercise protocol Exercise Sprint Drop-jumps Leg extension Sprint (continued) ( 2018a ) ( 2019 ) et al. ( 2016b ) et al. ( 2017 ) Cocking et al. et al. Cocking 3 Table References Grifn et al. Page et al. ( 2017 ) et al. Page Paradis-Deschenes Paradis-Deschenes Zinner et al. Zinner et al.

1 3 European Journal of Applied Physiology (2019) 119:2123–2149 2133 (%) LA (%) MA 2 2 5 km TT LA output LA Power (%) LA TSI Mean HR MA MA Mean SV Mean Q MA Δ [HHb] MA Δ [THb] MA RPE MA SpO 5 km TT MA output MA Power (%) MA TSI Mean TSI (%) Mean TSI Hb Total deoxyHb Avg Variable analyzed Variable Mean HR LA LA Mean SV Mean Q LA Δ [HHb] LA Δ [THb] LA RPE LA SpO race On-ice 1000 m Test protocol Test Time trialTime 5 km 60 min Time to test to Time 25.6 ± 0.7 min (IPC) Arms: 30 > SAP 10 mmHg (P) Ischemia pressure pressure Ischemia (mmHg)/limb 220/thighs (IPC) 20/thighs (P) P/IPC Group P/IPC 3 × 5 min/15 min IPC protocol IPC time Total 3 × 5 min/15 min 9 13 N Speed skaters Participants Road cyclists Road Mountain bikers Triathletes Ice race Exercise protocol Exercise Cycling (continued) laut ( 2018 ) et al. ( 2018 ) et al. Richard and Bil - Richard 3 Table References Paradis-Deschenes Paradis-Deschenes

1 3 2134 European Journal of Applied Physiology (2019) 119:2123–2149 ) −1 (l min 2 3 2 mVO (%) 2 HCO SO Variable analyzed Variable Time 100 m (s) Time 200 m (s) Time count 50 m Stroke 50 m rate Stroke count 100 m Stroke 100 m rate Stroke Blood lactate TCO Test protocol Test 100 m 200 m Time to test to Time 2 h or 24 h (IPC) Ischemia pressure pressure Ischemia (mmHg)/limb 160–228 thighs 15 thighs (P) Group P/IPC exercise capacity, capacity, exercise capacity 2, Ex. Wingate power 2 mean Pw. 1, Mean Wingate mean power Pw1 mean IPC protocol IPC time Total 4 × 5 min/20 min 20 N the study did not provide P value enough dataprovide calculate efect size (ES), α thedid not to study provide , Ω thedid not study 2 O cardiac phosphocreatinine-to-adenosine-triphosphate cardiac PESM PCr ratio, ratio PCr/ATP kinase; B [La] blood lactate creatine Cardiac concentration, Participants Swimmers maximal power in Wingate, Wingate, in power maximal Pw. Max. 2max 2max percentage of hemoglobin containing of hemoglobin percentage Exercise protocol Exercise Swimming 2 maximal iso - MIVC peak concentration, Muscle Hb peak conc. muscle hemoglobin concentration, average conc. muscle hemoglobin Muscle Hb avg. conc concentration, average; ischemic preconditioning, CMJ preconditioning, group P placebo group without C control with jump, VJ vertical IPC ischemic cuf administration, a sham intervention, peak power, jump VJPP vertical Avg , 2 (continued) T. 1000 m 1000 m; to time T. V O ( 2018 ) Peak heartPeak (bpm) 30% V O rate Average heart (bpm) 30% V O rate Average

time to time to T.Fat. index, fatigue index Fat. tolerance, exercise toler. Exer. exhaustion, time to Exhaust. preconditioning, P placebo, IPC ischemic C control, peak power, jump VJPP vertical fatigue, 3 Table a References mean b respiratory E. ratio Resp. of total hemoglobin, in concentration Δ [HHb] changes of deoxy-hemoglobin, in concentration metric voluntaryΔ [THb] changes DOMS muscle soreness, contraction, SmO ratio, exchange squat jump, CK jump, SJ squat jumps, countermovement electromyography of quadriceps muscle, GXT 1 graded Blood [La] peak blood lactate Quadriceps concentration, EMG electromyography recovery, muscle phosphocreatine skeletal post-exercise recovery scale; Ext. muscle soreness Scale perceived Soreness status scale, Perc. recovery Scale perceived Rec.Stat. Perc. exertion, of perceived RPE rating 2; test 1, GXT 2 graded test exercise exercise extension; Williams et al. et al. Williams

1 3 European Journal of Applied Physiology (2019) 119:2123–2149 2135 SWC 0.6 SWC No No No No No No No No No No No No No No No No No No Ω No No Ω No No No No No No No Yes No No No No No Achievement 0.2 SWC No Yes No Yes Yes Yes Yes No No No No No No No No No No No Ω No No Ω No No Yes No No No Yes Yes No No No No Yes Mean diference between between Mean diference - interven IPC and control tion 1.6 105.2 0.6 6 5 6 10.3 − 34 0 − 7.56 0 4.79 1.0 0.0 0.2 − 14 − 0.55 38.6 Ω 0.3 − 0.67 Ω − 0.03 0.3 − 0.03 2.0 − 0.05 − 9.7 9 48 − 0.8 − 20 − 21 − 21 19 SWC (SD × 0.6) SWC 4.1 154.0 2.6 6.7 6.9 37.2 26.4 87.6 38.8 149.1 2.4 71.4 74.4 0.2 1.3 129.6 6.5 167.2 6.7 3.1 3.7 8.4 0.1 7.2 0.1 5.4 0.2 0.0 9.6 43.2 2.2 13.2 9.6 9.0 39.6 SWC (SD × 0.2) SWC 1.4 51.3 0.9 2.2 2.3 12.4 8.8 29.2 12.9 49.7 0.8 23.8 24.8 0.1 0.4 43.2 2.2 55.8 2.3 1.0 1.2 2.8 0 2.4 0 1.8 0.1 6.8 3.2 14.4 0.7 4.4 3.2 3.0 13.2 ES 0.25 0.32 0.13 0.54 0.42 0.10 0.22 − 0.26 0 − 0.03 0 0.04 0.01 0.00 0.09 − 0.07 − 0.06 0.11 0.5 0.06 − 0.11 1.3 0.2 − 0.26 0.16 − 0.20 0.18 0.32 0.60 0.86 0.22 0.93 1.35 1.35 0.28 values and efect sizes 0.6), P values × P 0.003 NS NS < 0.05 < 0.05 0.05 < 0.05 NS NS 0.48 NS NS NS 0.40 NS NS 0.67 NS NS NS 0.03 NS NS NS NS NS NS 0.03 < 0.05 < 0.05 < 0.05 < 0.05 < 0.01 < 0.01 < 0.05 0.2 and SD × Change (%) Change 2.8 3.6 1.2 − 5.1 − 4.4 1.6 3.7 2.5 0.0 − 0.7 0.0 − 0.3 0.0 0.6 1.0 2.6 − 1.1 1.6 4.1 0.9 1.1 − 1.0 1.1 0.7 − 0.3 9 0.0 7.0 8.2 − 17.2 0.4 − 2.2 − 2.8 − 2.9 10.6 b a HR HR 2max 2max 2max Variable analyzed Variable Max power Workload trialTime Peak Ex. toler. Peak power Peak V O Heart rate Time trialTime CK Mean power Exhaust. time Exhaust. Fat. index Fat. VJPP SJ (w) VJ Time trialTime V O CMJ (w) Time V O 10 m sprint 40 m sprint Avg. Avg. Time trialTime Time Time T. 1000 m T. Max Pw. 1 Max Pw. Mean Pw. 1 Mean Pw. Mean Pw. 2 Mean Pw. T. Fat T. All papers data with statistical results: calculated values of SWC (SD of SWC All papers data withcalculated values results: statistical 4 Table References de Groot et al. ( 2010 ) et al. de Groot Barr ( 2011 ) Foster et al. ( 2011 ) et al. Foster ( 2013 ) et al. Cochrane Beaven et al. ( 2012 ) et al. Beaven Jean-St-Michel et al. ( 2011 ) et al. Jean-St-Michel Crisafulli ( 2011b ) et al. Gibson et al. ( 2013 ) Gibson et al. Bailey et al. ( 2012b ) et al. Bailey Clevidence et al. ( 2012 ) et al. Clevidence Foster et al. ( 2014 ) et al. Foster Kjeld et al. ( 2014 ) Kjeld et al. Paixao et al. ( 2014 ) et al. Paixao Barbosa et al. ( 2015 ) Barbosa et al.

1 3 2136 European Journal of Applied Physiology (2019) 119:2123–2149 SWC 0.6 SWC No No No No Ω No No No No No No No No No No No No No No No No No No No Ω Ω Ω Ω No No No No Achievement 0.2 SWC No Yes No No Ω No No Yes Yes No No No Yes No No No No No No No No Yes Yes No Ω Ω Ω Ω No Yes No No 0.1 − 0.12 − 0.02 Mean diference between between Mean diference - interven IPC and control tion 0.11 Ω 0 4.5 0.6 0.5 0 − 0.8 – 0.2 − 34.3 − 0.15 0 − 173.4 − 0.68 − 3 5 − 2.4 11 10 − 0.84 Ω Ω Ω Ω 2 0.3 0.5 36 0.2 0.5 0.2 SWC (SD × 0.6) SWC 0.7 Ω 0.2 43.1 0.7 1.2 6 1.3 – 0.3 221.2 0.5 4.2 848.2 0.4 6.6 16.2 2.7 25.7 23.4 0.6 Ω Ω Ω Ω 7.2 0.5 5.6 124.8 0.1 0.2 0.1 SWC (SD × 0.2) SWC 0.2 Ω 0.1 14.4 0.2 0.4 2 0.5 – 0.1 92.3 0.2 1.4 342.4 0.1 2.2 5.4 0.9 8.6 7.8 0.2 Ω Ω Ω Ω 2.4 0.2 1.9 41.6 0.29 0.12 0.07 ES 0.1 Ω 0 0.07 0.5 0.26 0 − 0.33 – 0.44 − 0.08 − 0.19 0 − 0.11 − 0.97 − 0.27 0.15 − 0.52 0.26 0.29 − 1.02 Ω Ω Ω Ω 0.17 0.15 0.35 0.06 0.18 Α NS NS P 0.04 0.01 0.937 NS 0.07 0.111 NS NS 0.017 NS NS 0.36 0.77 NS 0.04 NS NS 0.02 0.001 NS 0.31 NS NS NS NS 0.567 < 0.05 0.529 0.862 Α 3.8 − 3.3 − 0.6 Change (%) Change 2.9 8 0 − 0.7 7.5 3.8 0 − 11.8 9.7 9.5 − 0.4 − 0.5 0 − 1.2 − 1.9 − 8.8 1.5 − 1.2 2 3.8 − 10.1 1.1 0.0 2.3 1.8 3.125 1.4 17.6 0.9 2.3 ) ) ) −1 −1 −1 (l min 2 (l min peak 2 2 2max Variable analyzed Variable Time to exhaustion to Time Time to 5 km to Time Speed (m s m V O Blood [La] V O Blood [La] peak Aerobic capacity Aerobic Blood [La] Quadriceps EMG Cardiac PCr/ATP ratio PCr/ATP Cardiac Peak power Peak Sprint time (best) Blood pressure Total power Total Sprint time (worst) PESM PCr recovery Ex. capacity Sprint time (total) Mean power output Mean power Ex. capacity Sprint time (decr.) V O Peak power Peak Mean power Peak power Peak Mean power Heart rate Time trialTime Blood [La] Overall fatigue index fatigue Overall Peak power Peak V O (continued) 4 Table References Cruz ( 2015 ) et al. Tocco et al. ( 2015 ) et al. Tocco Banks et al. ( 2016 ) Banks et al. Gibson et al. ( 2015 ) Gibson et al. Ferreira ( 2016 ) et al. Hittinger et al. ( 2015 ) et al. Hittinger Cruz ( 2016 ) et al. Lalonde and Curnier ( 2015 ) Martin ( 2015 ) et al. Marocolo et al. ( 2015 ) et al. Marocolo Patterson et al. ( 2015 ) et al. Patterson

1 3 European Journal of Applied Physiology (2019) 119:2123–2149 2137 SWC 0.6 SWC No No No No No Yes No No No No No No No No No No No No No No No Yes Yes Yes No Yes Yes Yes Achievement 0.2 SWC No No Yes No No Yes No No No No Yes No Yes No No No No No No Yes No Yes Yes Yes Yes Yes Yes Yes Mean diference between between Mean diference - interven IPC and control tion − 4 0.5 0.4 0 − 0.1 32 − 0.9 0.1 0.01 − 3.4 0.6 0.2 0.6 − 0.3 − 6.4 − 0.07 − 13 − 1 0 0.7 − 1.3 45 230 47 6.8 6.4 35 7.9 SWC (SD × 0.6) SWC 6 2.2 0.7 6 0.6 25.2 9.7 0.7 0 10.8 0.9 0.7 1.3 1.1 8.3 0.5 21.6 3.6 4.2 1.1 1.4 25.7 228 22.8 9.5 2.7 18.7 7.1 SWC (SD × 0.2) SWC 2 0.7 0.2 2 0.2 8.4 3.2 0.2 0 3.6 0.3 0.22 0.4 0.4 2.8 0.2 7.2 1.2 1.4 0.4 0.5 8.6 76 7.6 3.2 0.9 6.2 2.4 ES − 0.4 0.16 0.33 0 − 0.09 0.58 − 0.06 0.08 0.11 − 0.2 0.36 0.17 0.26 − 0.14 − 0.32 0.05 − 0.31 − 0.15 0.00 0.42 − 0.62 0.91 0.54 1.12 0.43 1.38 1.12 0.65 P 0.01 0.436 0.021 0.74 – 0.166 0.67 – 0.21 0.125 0.32 0.78 0.9 0.098 0.46 0.015 0.003 ≤ 0.05 ≤ 0.05 0.40 0.27 Α Α Α Α Α 0.001 0.01 Change (%) Change − 6.7 0.9 2.67 0 − 0.73 9.2 − 0.44 0.86 1 − 1.52 11.3 2.3 4.3 − 4.6 − 20.2 − 0.53 4.8 − 2.7 0.0 13.7 − 29.5 8.5 12.9 13.3 10.6 8.5 17.7 29.2 (GXT1) (GXT2) rate rate 2max 2 Variable analyzed Variable Heart Running speed: 4 mmol Running run time Total economy Running Heart B [La]: 2 mmol v V O Caloric unit cost Running economy Running Blood [La] V O RPE Number of repetitions Number Blood [La] Fatigue index Fatigue Number of repetitions Number Peak torque Peak SJ mean jump height SJ mean jump Mean CMJ height Perc. Rec. Stat. Scale Stat. Rec. Perc. Perc. Soreness Scale Soreness Perc. Peak knee ext. force knee ext. Peak Tot. knee ext. force knee ext. Tot. Avg. knee ext. force knee ext. Avg. Muscle Hb avg. conc Muscle Hb avg. Muscle Hb peak conc Time to fatigue to Time Muscle oxygenation (continued) et al. 2016 ) et al. ( 2016b ) 4 Table References James et al. ( 2016 ) James et al. Kaur et al. ( 2017 ) Kaur et al. Marocolo et al. ( 2016b ) et al. Marocolo Marocolo et al. ( 2016a ) et al. Marocolo IPC-post exercise (Northey (Northey exercise IPC-post Paradis-Deschenes et al. et al. Paradis-Deschenes Tanaka et al. ( 2016 ) et al. Tanaka

1 3 2138 European Journal of Applied Physiology (2019) 119:2123–2149 SWC 0.6 SWC No Yes No No No No No No No No No Yes No No No No No No No No No No No Yes No Yes No No Yes No No Achievement 0.2 SWC Yes Yes No No Yes No No No No No No Yes Yes No No No No Yes No No Yes No No Yes No Yes No No Yes Yes No 0.2 0.2 Mean diference between between Mean diference - interven IPC and control tion − 0.7 − 0.12 − 1 0 3 − 0.3 − 0.01 0 7 0.8 0 0.4 0 − 0.4 − 19 0.3 0 − 0.3 1.6 − 6 − 15 8.9 0.4 4.5 − 49.1 − 300.6 19.92 0.74 − 12.54 1.1 1.1 SWC (SD × 0.6) SWC 2.6 1.3 1.8 1.8 21 7.6 0 0 40.2 0.8 0.2 0.3 3.0 0.2 67.2 0.8 1.2 1.8 1.9 127.2 67.2 4 2.6 3.9 18.1 180.1 17.3 6.0 4.0 0.4 0.4 SWC (SD × 0.2) SWC 0.9 0.4 0.6 0.6 7 2.5 0 0 13.4 0.3 0.1 0.1 1.0 0.1 22.4 0.3 0.4 0.6 0.6 42.4 22.4 1.3 0.9 1.3 6 60 5.8 0.2 1.3 0.11 0.12 ES − 0.15 − 0.06 − 0.33 0 0.08 − 0.02 − 1 0 0.1 0.47 0 0.73 0 − 1 − 0.18 0.25 0 − 0.1 0.55 − 0.03 − 0.13 1 0.11 0.8 − 1.8 − 1.5 0.67 0.92 − 1.3 0.92 0.17 P 0.1 0.719 0.1 0.71 0.99 0.83 0.42 0.8 0.111 0.212 0.82 0.37 0.17 0.26 0.3 0.69 0.6 0.19 0.24 0.1 0.3 NS 0.69 NS < 0.05 0.78 NI NI NI 0.3 0.3 Change (%) Change − 1.3 1.1 − 0.5 0 1.05 − 0.5 − 0.9 0 3 6.7 0 4.5 0 − 4.3 1.3 3.4 0 − 2.6 28.2 − 0.7 1 10.9 3.5 5.6 − 46.3 − 47.2 4.8 14.1 − 18.1 consumed 2 (incremental test) test) (supramaximal O 2max 2max 2 Variable analyzed Variable V O Heart (incremental rate test) test) HR (supramaximal Power (avg) Power Total work done work Total RER (incremental test) test) RER (supramaximal Critical power Blood [La] Blood [La] (Icremental Test) test) Blood [La] (supramaximal Total Total Heart Rate Borg (incremental test) Borg Time Trial Time RPE V O RPE Blood [La] Blood [La] Distance Time trialTime 24 h MIVC Blood [La] CMJ V O DOMS CK Average force Average Δ [THb] Δ [HHb] (continued) ( 2016b ) 4 Table References Sabino-Carvalho et al. ( 2017 ) Sabino-Carvalho et al. Grifn ( 2018 ) et al. Marocolo et al. ( 2017a ) et al. Marocolo Seeger et al. ( 2017 ) et al. Seeger Page et al. ( 2017 ) (Post) et al. Page Cocking et al. ( 2017 ) et al. Cocking Paradis-Deschenes et al. et al. Paradis-Deschenes

1 3 European Journal of Applied Physiology (2019) 119:2123–2149 2139 SWC 0.6 SWC No No Yes No No No No No Yes No No No Yes No No No No No No No No No No No No No No No No No No No No Achievement 0.2 SWC No No Yes Yes No Yes No No Yes No No No Yes No No No No No No No No No No No No No No No No No No No No Mean diference between between Mean diference - interven IPC and control tion − 0.5 0 49.64 3.4 − 5.1 4.75 − 3 − 0.6 0.78 0.18 0.02 0.9 4.84 − 0.06 1.28 0.1 0 0 − 0.6 − 0.08 − 3 − 0.3 0 0.6 0.01 − 3 0.35 − 1.4 0.6 0 0 0.5 − 0.2 SWC (SD × 0.6) SWC 1.0 1.1 20.4 10.3 12.4 10.3 12.4 4.7 0.6 0.9 0.0 4.4 3.7 0.4 4.0 2.0 0.9 0.1 2.9 0.4 18.5 3.4 0.1 6.6 0.0 18.5 4.0 6.6 2.9 3.4 4.5 4.5 1.7 SWC (SD × 0.2) SWC 0.3 0.4 6.8 3.4 4.1 3.4 4.1 1.6 0.2 0.3 0 1.5 1.2 0.1 1.3 0.7 0.3 0 1.0 0.1 6.2 1.1 0 2.2 0 6.2 1.3 2.2 1.0 1.1 1.5 1.5 0.6 ES − 0.28 0 1.3 0.2 − 0.26 0.26 − 0.16 − 0.08 0.7 0.1 0.4 0.1 0.94 − 0.08 0.2 0.03 0 0 − 0.1 − 0.1 − 0.1 − 0.05 0 0.05 0.2 − 0.1 0.06 − 0.1 0.1 0 0 0.07 − 0.08 P 0.693 0.693 NI > 0.05 > 0.05 > 0.05 > 0.05 0.538 NI 0.5 0.91 0.261 NI 0.99 < 0.005 0.7 0.5 0.92 0.4 0.99 0.99 0.91 0.92 0.86 0.09 0.99 < 0.005 0.86 0.4 0.91 0.538 0.261 0.7 Change (%) Change − 3 0 8.9 5.6 − 10.1 7.8 − 5.9 − 0.5 12.7 1.1 4.2 − 5.8 6.2 − 1.9 16.1 0.8 0 0 − 2.8 − 2.6 − 2.7 − 1.2 0 0.3 2.1 − 2.7 4.4 − 0.8 2.8 0 0 − 2.8 − 1.6 ge ge RPE RPE during recovery during sprint during recovery during sprint 2 2 2 2 Variable analyzed Variable Average force Average Total sprint time Total Δ [THb] SmO SmO Mean time resp. diameter Peak Mean muscle oxy Δ [HHb] Oxygen uptake Oxygen Blood velocity Mean blood [La] Mean time Resp. E. ratio Resp. 30 s force Mean Oxygen uptake Oxygen Ventilation force Peak Resp. E. ratio Resp. Heart rate Peak diameter resp. diameter Peak Ventilation SmO Blood velocity Heart rate 30 s force SmO Peak force Peak Total sprint time Total Mean muscle oxy Mean blood [La] Mean (continued) ( 2016b ) 4 Table References Paradis-Deschenes et al. et al. Paradis-Deschenes Grifn ( 2018 ) et al. Zinner et al. ( 2017 ) Zinner et al. ( 2018a ) et al. Cocking Zinner et al. ( 2017 ) Zinner et al. Cocking et al. ( 2018a ) et al. Cocking Grifn ( 2018 ) et al.

1 3 2140 European Journal of Applied Physiology (2019) 119:2123–2149 SWC 0.6 SWC Yes Ω Ω No Ω Ω Yes No Yes No Ω Ω No No No No No No No No No No No No Achievement 0.2 SWC Yes Ω Ω Yes Ω Ω Yes Yes Yes No Ω Ω No No No No No Yes No Yes No No No No Mean diference between between Mean diference - interven IPC and control tion 5.7 0.9 − 0.1 3.6 − 7.3 − 5.2 1.3 6.7 7.5 0.1 − 2 − 0.9 0.1 − 0.72 − 3.4 0 1.6 7.05 0.4 0.69 0.08 − 2.8 − 1.8 − 0.3 SWC (SD × 0.6) SWC 2.4 Ω Ω 5.8 Ω Ω 1.0 7.6 6.7 4.3 Ω Ω 1.0 4.4 2.0 0.2 16.0 8.2 10.4 1.5 3.3 7.2 1.0 0.2 SWC (SD × 0.2) SWC 0.8 Ω Ω 1.9 Ω Ω 0.3 2.5 2.2 1.4 Ω Ω 0.3 1.5 0.7 0.1 5.3 2.7 3.5 0.5 1.1 2.4 0.3 0.1 ES 1.75 Ω Ω 0.39 − 0.38 − 0.22 0.84 0.34 0.75 0.01 Ω Ω 0.06 − 0.09 − 0.98 0 0.06 0.54 0.02 0.3 0.01 − 0.24 − 1.1 − 0.86 P NI NI NS NI NI 0.01 NI NI 0.51 NI NI NS NI NI NI NS NI NI NI NI NI NI NI NI Change (%) Change 3.4 1.1 − 0.1 2.3 − 1.5 − 1.1 4.9 2.3 2.4 0.1 − 5.5 − 2.3 1.9 − 1.5 − 2 0 1.9 4.2 0.8 2.4 0.1 − 3 − 25 − 4 (%) (MA) (%) (LA) 2 2 Variable analyzed Variable Mean HR (LA) Mean SV (LA) Mean SV 5 km TT (MA) 5 km TT (LA) Mean Q (LA) Power output (MA) Power Power output (LA) Power Δ [HHb] (LA) TSI (%) (MA) TSI TSI (%) (LA) TSI Δ [THb] (LA) Mean TSI (%) Mean TSI Mean HR (MA) RPE (LA) Total Hb Total Mean SV (MA) Mean SV SpO Avg.[THb] Mean Q (MA) On-ice 1000 m TT Δ [HHb] (MA) Δ [THb] (MA) RPE (MA) SpO (continued) ( 2018 ) 4 Table References Paradis-Deschenes et al. et al. Paradis-Deschenes Richard and Billaut ( 2018 ) Richard

1 3 European Journal of Applied Physiology (2019) 119:2123–2149 2141 ) −1 SWC 0.6 SWC No No Yes No No No No No No No No No No No No No No No No No (l min 2 Achievement 0.2 SWC No No Yes Yes No No No No No No No No No No No No No No No No Mean diference between between Mean diference - interven IPC and control tion − 1.35 − 0.04 21.45 3.15 0 − 0.36 0.27 − 2.5 − 0.27 − 0.5 − 0.94 − 1.4 − 0.9 − 0.9 − 1.9 − 0.2 − 1.1 0.46 − 0.4 0 SWC (SD × 0.6) SWC 4.6 3.4 4.6 3.4 4.9 1.2 1.2 6.2 4.9 1.4 6.2 4.8 1.4 1.9 4.8 4.3 1.9 2.4 4.3 2.4 SWC (SD × 0.2) SWC 1.5 1.1 1.5 1.1 1.6 0.4 0.4 2.1 1.6 0.5 2.1 1.6 0.5 0.6 1.6 1.4 0.6 0.8 1.4 0.8 ES − 0.23 − 0.01 2.68 0.43 0 − 0.19 0.13 − 0.24 − 0.03 − 0.2 − 0.08 − 0.17 − 0.36 − 0.28 − 0.04 − 0.03 − 0.32 0.12 − 0.01 0 P < 0.001 < 0.001 < 0.001 < 0.001 0.995 < 0.001 < 0.001 0.405 0.995 0.56 0.405 0.72 0.56 0.57 0.72 0.99 0.57 < 0.001 0.99 < 0.001 Change (%) Change 11.7 0.3 − 185.7 − 27.1 0 − 180 135 − 1.9 − 0.4 − 2.6 − 0.7 − 3.1 − 4.7 − 4 − 4.2 − 0.5 − 4.9 3.7 − 0.9 0 the study did not provide P value enough dataprovide calculate efect size (ES), α thedid not to study provide , Ω thedid not study 2 O cardiac phosphocreatinine-to-adenosine-triphosphate cardiac PESM PCr ratio, ratio PCr/ATP kinase, B [La] blood lactate creatine Cardiac concentration, 3 3 2 2 (%) (%) 2 2 2max Variable analyzed Variable Time 100 m (s) Time HCO SO HCO SO Time 200 m (s) Time Time 100 m (s) Time Stroke count 50 m Stroke Time 200 m (s) Time Stroke rate 50 m rate Stroke Stroke count 50 m Stroke Stroke count 100 m Stroke Stroke rate 50 m rate Stroke Stroke rate 100 m rate Stroke Stroke count 100 m Stroke Blood [La] Stroke rate 100 m rate Stroke TCO Blood [La] TCO 2max percentage of hemoglobin containing of hemoglobin percentage 2 maximal MIVC peak concentration, Muscle Hb peak conc. muscle hemoglobin concentration, average Conc. muscle hemoglobin Muscle Hb avg. Conc concentration, average, ischemic preconditioning, CMJ preconditioning, group P placebo group without C control with jump, VJ vertical IPC ischemic cuf administration, a sham intervention, peak power, jump VJPP vertical Avg , 2 (continued) exercise capacity, mVO capacity, 2, Ex. capacity exercise Wingate 2 mean power 1, Mean Pw. Wingate Mean Pw1 mean power in Wingate, maximal power 1000 m 1000 m, time to Max. Pw. T. V O Peak heartPeak (bpm) 30% V O rate Average heart (bpm) 30% V O rate Average

a 4 Table References Williams et al. ( 2018 ) (2 h) et al. Williams mean b squat jump, CK jump, SJ squat jumps, countermovement electromyography of quadriceps muscle, GXT 1 graded Blood [La] peak blood lactate Quadriceps concentration, EMG electromyography recovery, muscle phosphocreatine skeletal post-exercise recovery scale, Ext. muscle soreness Scale perceived Soreness status scale, Perc. recovery Scale perceived Stat. Rec. Perc. exertion, of perceived 2, RPE rating test 1, GXT 2 graded test exercise exercise extension; - respira E. ratio Resp. of total hemoglobin, in concentration Δ [HHb] changes of deoxy-hemoglobin, in concentration isometric Δ [THb] changes voluntary DOMS muscle soreness; contraction; SmO ratio, tory exchange Williams et al. ( 2018 ) (24 h) et al. Williams time to T.Fat. index, fatigue index Fat. tolerance, exercise toler. Exer. exhaustion, time to Exhaust. preconditioning, P placebo, IPC ischemic C control, peak power, jump VJPP vertical fatigue,

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◂Fig. 3 Forest plot of perceptual (rating of perceived exertion—RPE) not report any follow-up analysis of the participants in the and performance variables. a RPE; b jump; c power; d stroke rate; studies (e.g., no information about a potential interruption e time trial and sprint. Values shown are efect sizes with 95% confdence intervals. SD standard deviation, IV inverse variance, Std. of the IPC protocol, due to discomfort). However, all experi- standard, CI confdence interval, df degrees of freedom. Note: it is mental designs were cross-sectional, which may explain this possible to have a single study repeated multiple times if such study lack of information. In addition, all of these studies failed to presented numerous comparisons (e.g., IPC vs., SHAM; IPC vs., con- reference at least one of the relevant issues for experimental trol; time-course of comparisons) studies, such as the study design (randomized, double-blind study), a description of the study dropouts or relocation of it could be noted the statistical parameters related to IPC the participants. efects (i.e., P value, ES and SWC). Forty-fve studies were included in this meta-analysis. Time between IPC and exercise or test and general Across all included studies, the results indicate low hetero- characteristics of IPC protocols geneity (I2 = 0%; Z = 0.33–1.37; P > 0.05; Figs. 3, 4). The frst attempts to evaluate the IPC efects on exercise performance applied the tests immediately after the maneu- Discussion ver, probably to take advantage of the period of reactive hyperemia (Nukada 1955; Muller 1958; Collier and Percival The aim of this review was to interpret the application of 1959; de Groot et al. 2010). However, more recent studies IPC on exercise performance using both traditional statistics have used an interval time of up to 45 min (Bailey et al. (P value and ES) and SWC approach in healthy individuals. 2012b; Hittinger et al. 2015; Jean-St-Michel et al. 2011; The main fnding was that IPC promotes a small magni- Zinner et al. 2017), 60 min (Seeger et al. 2017; Richard and tude of benefcial efects, alternated with null or detrimental Billaut 2018), 90 min (Higgins and Thompson 2002; Barr efects. The selected studies presented high quality; however, 2011) or up to 24 h (Beaven et al. 2012; Cochrane et al. most of them did not describe statistical signifcance in the 2013; Banks et al. 2016; Northey et al. 2016; Page et al. measured performance or physiological variables. Seven 2017) in some studies. Short intervals (i.e., less than 10 min) studies reported signifcant benefcial and one detrimental between IPC and exercise promoted benefcial (Bailey et al. efects of IPC. Among these studies, only one included a 2012b; Singh et al. 2017; James et al. 2016) and detrimental placebo/sham group in their experimental design to control efects (Paixao et al. 2014; Tocco et al. 2015), as well as a potential placebo/nocebo efect from the experiments, and long intervals (i.e., more than 30 min) when faster swim- this faw could have generated biased results. Therefore, con- ming time or higher cycling power (Jean-St-Michel et al. sidering the SWC analysis, the current data showed trivial or 2011; Patterson et al. 2015) and less peak torque (Northey non-positive efect from the IPC intervention. et al. 2016) were found. Interestingly, intervals of more than 45 min promoted less detrimental efects compared to shorter ones, which could speculate that IPC efects requires Quality of the papers a minimal time window. The most common IPC applied protocol is three (17 stud- The general mean score for quality was 81%. Most part of ies) of four (20 studies) cycles of 5 min ischemia followed by the assessed studies showed some limitations: Only 11 stud- 5 min reperfusion. Other protocols, such as 2 cycles of 3 min ies included the CI for the main results (criterion 14). This ischemia and 30 s alternating were also found in two studies. is particularly important, because the CI is infuenced by the Interestingly, benefcial IPC efect with statistical diference sample size, the homogeneity of the data sample, and the (P < 0.05) occurred in six studies that applied the 3 × 5 min confdence level selected by the researcher. The CI is based protocol, while only in one study that used 4 × 5 min proto- on the fact that there is a sampling error, which depends col. It seems that at least three cycles of ischemia, with no on how well the statistics represent the target population. more than fve minutes promotes the best benefcial efects Therefore, a report of the CI values provides a range, not a on exercise performance. single point, which likely includes the estimate of the average of the population. Nine further studies lacked informa- Exercise and test modalities tion about quality criterion, which referred to reports of the actual probability values. Reporting the exact P value Sixteen experiments performed cycling tests, with 10 of provides more information about the strength of the evi- these involving incremental or time-trial eforts and six dence against the null hypothesis and allows each reader anaerobic cycling sprints (6–30 s duration). Time-trial run- to reject it. Finally, there were defciencies with regard to ning was used in six studies, while fve evaluated sprints quality criterion in eight studies. Specifcally, 18 studies did and one a YOYO intermittent test. Swimming of 100 m

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Fig. 4 Forest plot of physiological variables. a Heart rate (HR); b lac- it is possible to have a single study repeated multiple times if such tate (Lac); c oxygen uptake (VO2). Values shown are efect sizes with study presented numerous comparisons (e.g., IPC vs., SHAM; IPC 95% confdence intervals. SD standard deviation, IV inverse variance, vs., control; time-course of comparisons) Std. standard, CI confdence interval, df degrees of freedom. Note:

1 3 European Journal of Applied Physiology (2019) 119:2123–2149 2145 and 200 m time trial were found in three studies and also representative power of the experiment is also presented. dynamic and static apnea were tested. The most signifcant Figure 4 shows in part a similar null IPC efect or in most results of IPC are found in cycling modalities, maybe due part of studies, a favor efect to placebo/sham/control is to specifcity of test or sensitivity of measured parameters, depicted. Therefore, although IPC has shown some benef- while only two studies reported signifcant benefcial efects cial efects on exercise performance, under the view of SWC, using a real-world exercise, one running and skating. Most our data do not support IPC as an efective ergogenic aid. of the experiments carried out a laboratory test, which could On the other hand, perhaps, the optimal IPC protocol per si interfere on the results, minimizing the real IPC efects. In (e.g., number of cycles of ischemia–reperfusion and time to this context, it is relevant to highlight that what happens start the exercise) has not been found yet, and future studies during real training or competition is quite diferent from should explore it. the artifcial setting of a laboratory (Buchheit 2016b, 2017). We have excluded 86 non-English language studies from Therefore, the current results could not be easily transferred the current review, being 17 of these classifed as reviews. to real-world settings of athletes/competitions even if posi- From the 69 remaining papers, we have excluded 67 by title tive and meaningful fndings were confrmed (Marocolo or abstract. Therefore, two papers could have some inter- et al. 2018). esting content about IPC and exercise performance, but no abstract information could be found for both manuscripts. Fitness level of participants The frst one was written in German (year date 1969; it was not possible to identify the exact author due the similarity It is largely known that training level of participants is of surnames) and another written in Slovak (year date 1986; directly related to results analysis. Just two studies selected we have sent an email to correspondent author requesting for this review presented high fitness level participants that paper but we had no answer). While there are reports (based on physiological and performance parameters, e.g., in the scientifc literature, showing that this exclusion does VO2max, time-trial): Richard and Billaut (2018) tested elite not impact the fnal fndings of systematic reviews (Morrison speed skaters, while Paradis–Deschenes analysed cyclists et al. 2012; Juni et al. 2002), we acknowledge it might be a (Paradis-Deschenes et al. 2018). All other studies included limitation. amateur or recreational participants, even when the title or some part of the text mentioned "highly trained". The lack IPC‑induced mechanisms on exercise performance of studies including elite athletes is understandable, because the natural limitations to do that. However, the reader should Although the current study is a meta-analysis, the selected be aware of a minor SWC could be relevant for an elite ath- papers overall lack investigating the physiological mecha- lete but not for a recreational one. nisms. The physiological mechanisms underlying a potential ergogenic efect from IPC on exercise performance are IPC efects in view of SWC and ES unclear and we have discussed some insights from the literature briefy. Thirteen studies (~ 29%) reported results achieving 0.2 SWC A lower perception of fatigue could explain the better for performance parameters, while fve (~ 11%) achieved endurance performance found in some studies. IPC could 0.6 SWC. Based on statistical proposals, for amateur or rec- desensitize group III and IV nerve endings to metabolite reational ftness level of participants, the 0.6 SWC should accumulation, since type III and IV nerve endings would be considered. In this hand, only two studies (Paradis- infuence cardiovascular function during exercise (Amann Deschenes et al. 2018; Richard and Billaut 2018) have evalu- et al. 2011), contributing to improvements in performance. ated elite athletes and did not achieve either 0.2 or 0.6 SWC Type III and IV nerves modulate the sympathetic tone on for performance parameters, although one of them reported the active muscle, stimulating type III mainly as mechano- signifcance statistical values (P < 0.05). At frst glance, this and IV as metabo-receptors (Nobrega et al. 2014), resulting analysis could suggest that IPC promote efects of low mag- in increases in sympathetic tone, regulating, for instance, nitude in most part of the studies and, when the magnitude cardiac contractility (Marongiu et al. 2013; Crisafulli et al. of efect is higher the ftness level of participants is lower. 2011a). Although IPC results showed more magnitude of efects in IPC-induced mechanisms are also related to local vasodi- lower trained participants, futures studies should test if IPC lation at moderate-intensity exercise (Horiuchi et al. 2015), response-interventions are related to ftness level. which may contribute to blood supply and consequently This fact is supported by the analysis of forest plot optimize the delivery of nutrients and oxygen to the periph- (Fig. 3), showing that performance variables are in most eral tissue, and muscle deoxygenation kinetics during exer- cases near to null mean diference the line and, if a favor cise (Kido et al. 2015). Then, increasing in blood fow and IPC/Placebo efect is noted, a large range follow and small muscle oxygenation (Barbosa et al. 2015; Paradis-Deschenes

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Eur J Appl Physiol version of the manuscript. 112(10):3649–3654. https://doi.org/10.1007/s00421-012-2345-5 Cochran WG (1954) The combination of estimates from diferent Compliance with ethical standards experiments. Biometrics 10:101–129 Cochrane DJ, Booker HR, Mundel T, Barnes MJ (2013) Does intermittent pneumatic leg compression enhance muscle recovery after Conflict of interest All authors declare that they have no confict of strenuous eccentric exercise? Int J Sports Med 34(11):969–974. interest. https://doi.org/10.1055/s-0033-1337944

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