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The Effects of Cardioplegia on Coronary Pressure–Flow Velocity

The Effects of Cardioplegia on Coronary Pressure–Flow Velocity

European Journal of Cardio-thoracic Surgery 16 (1999) 324±330 www.elsevier.com/locate/ejcts

The effects of on coronary pressure±¯ow velocity relationships during replacement

Xu Y. Jin, Derek G. Gibson, John R. Pepper* Downloaded from https://academic.oup.com/ejcts/article/16/3/324/479982 by guest on 29 September 2021 Departments of and , Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK Received 21 December 1998; received in revised form 31 May 1999; accepted 7 June 1999

Abstract Objective: The acute physiological response of the to aortic (AVR) has not been fully elucidated. This study aimed to characterize the changes in coronary pressure-¯ow velocity relationships, and to test whether this relationship is affected by cardioplegic method. Methods: Nineteen patients (mean age 67 ^ 12 (SD) years, 9 males) undergoing aortic valve replace- ment who received either cold blood cardioplegia (CBC, n ˆ 9) or warm blood cardioplegia (WBC, n ˆ 10), were prospectively studied before and 30 min after the operation, using transesophageal Doppler combined with high ®delity left ventricular (LV) and aortic pressures. We thus determined: (1) Diastolic ¯ow velocities in proximal anterior descending coronary (LAD), and simultaneous to LV pressure differences. (2) The slope (LAD proximal linear resistance) and pressure intercept (zero ¯ow pressure) of this relationship. (3) Overall LAD linear resistance as the ratio of mean diastolic ¯ow velocity to mean pressure difference between aorta and left . (4) LV myocardial work. Results: Following operation, myocardial stroke work fell from 5.2 ^ 2.7 to 3.0 ^ 1.7, mJ cm23 (P ˆ 0:001), LAD mean diastolic ¯ow velocity increased from 47 ^ 19 to 74 ^ 21, cm s21 (P ˆ 0:0002). LAD overall linear resistance fell (0.75 ^ 0.24 vs. 1.26 ^ 0.26, mmHg cm21 s, P ˆ 0:001). LAD proximal linear resistance, however, remained unchanged (P ˆ 0:21), but the zero ¯ow pressure fell (18 ^ 12.6 vs. 27 ^ 12.2, mmHg above LV end diastolic pressure, P ˆ 0:013). With similar fall in myocardial work postoperatively, there was a greater fall in zero ¯ow pressure after WBC than CBC (48 ^ 28 vs. 19 ^ 13,% of pre-op, P ˆ 0:012), and a greater increase in ¯ow velocity time integral (127 ^ 81 vs. 53 ^ 59,%, P ˆ 0:039). Conclusion: Instantaneous diastolic LAD pressure-¯ow velocity relations in the early postoperative period can be explained more satisfactorily in terms of zero ¯ow pressure and proximal linear resistance than simple resistance alone. The fall in zero ¯ow pressure alone explains the increase in LAD ¯ow velocity immediately after . The extent of this fall is greater after warm rather than cold blood cardioplegia. q 1999 Elsevier Science B.V. All rights reserved.

Keywords: Coronary pressure±¯ow velocity relationship; Aortic valve replacement; Cardioplegia;

1. Introduction may play an important role in determining ¯ow and thus the acute response of coronary circulation during cardiac The acute response of the coronary circulation to cardio- surgery. pulmonary bypass has been extensively investigated [1±4]. In the clinical setting, ¯ow velocities in the proximal Coronary resistance, calculated as the simple ratio of perfu- coronary can be reliably measured by transesopha- sion pressure to its ¯ow rate, has variably been found to rise geal echocardiography [8,9]. Changes in coronary ¯ow [2] or fall [3,4] immediately after cardiac surgery. These velocity pro®le several weeks after aortic valve replacement changes may be related to the diverse nature and extent of have been documented [10,11], but few studies have been coronary vascular injury by cardioplegia and reperfusion reported during the operation itself. We have previously [5]. The precise mechanisms underlying changes in coron- found that retrograde warm blood cardioplegia resulted in ary resistance remain incompletely understood. It is possible a less satisfactory protection of hypertrophic myocardium that the simple ratio of pressure to ¯ow may not adequately than cold blood cardioplegia [12]. However, it is not clear characterise coronary hemodynamics. Indeed, the existence whether the cardioplegia method also has an independent of a ®nite coronary zero ¯ow pressure [6,7], which is effect upon the coronary hemodynamic response. Taking assumed to be zero in the orthodox de®nition of resistance, advantage of the relative stability and accessibility of intra-operative conditions, we have combined measure- * Corresponding author. Tel./fax: 144-171-351-8530. ments of coronary artery ¯ow velocity with simultaneous E-mail address: [email protected] (J.R. Pepper)

1010-7940/99/$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. PII: S1010-7940(99)00216-X X.Y. Jin et al. / European Journal of Cardio-thoracic Surgery 16 (1999) 324±330 325 Brompton Hospital. Written informed consent was obtained from all participants. There was no early mortality, morbid- ity, or side effects due to this study. Patients were studied under general anesthesia, main- tained with fentanyl (20 to 50 mgkg21), pancuronium oxide (0.1 mg kg21). A Swan-Ganz thermodilution balloon tip catheter was positioned with its tip in the after induction of anesthesia and used for hemody- namic measurements. was routi- nely established using membrane oxygenator and roller pump, with hemodilution (hematocrit value 20-25%), and systemic hypothermia (288C nasopharyngeal temperature, when using cold blood cardioplegia, 9 patients), or with Downloaded from https://academic.oup.com/ejcts/article/16/3/324/479982 by guest on 29 September 2021 normothermia (378C), in 10 patients in whom continuous retrograde warm blood cardioplegia was given by a rando- mised approach which has been reported previously in detail [12].

2.2. Protocols

2.2.1. Measurement of coronary blood ¯ow velocity A 5 MHz biplane transesophageal echocardiographic transducer (HP 21362C) interfaced with a Hewlett Packard 77025A Sonos 500 or 1500 Ultrasound System was posi- Fig. 1. Simultaneous recordings of electrocardiogram, ¯ow velocity of left tioned after induction of anesthesia. From the transesopha- anterior descending coronary artery, and high ®delity pressures in left geal horizontal view at aortic valve level, the proximal left ventricle and aortic root from a representative patient, with paper speed anterior descending coronary artery (LAD) was located on 21 of 100 mm s . (A) Before cardiopulmonary bypass; (B) immediately after the two dimensional colour ¯ow image. LAD blood ¯ow aortic valve replacement. Note that there was a signi®cant increase in velocity was recorded by 5 MHz pulsed Doppler with the coronary ¯ow velocity after the operation, particularly in mid and late diastole. sample volume (1 mm) placed at its proximal one third, i.e. 2±3 cm distal to the bifurcation of anterior descending and perfusion pressure and myocardial stroke work, derived circum¯ex arteries [8,9]. Records were made at a paper from aortic and left ventricular (LV) micromanometers speed 100 mm s21 with simultaneous electrocardiogram, and simultaneous LV echocardiogram. This approach LV pressure and aortic root pressure, before the onset of enabled us to incorporate the waterfall approach in assessing cardiopulmonary bypass in a stable hemodynamic state, the acute effects of aortic valve replacement on the coronary and repeated 30 min after the cardiopulmonary bypass had pressure-¯ow velocity relationship, and the possible in¯u- been weaned off, with the chest still open (Fig. 1). ence of cardioplegic methods.

2.2.2. Measurement of ascending aortic and LV pressures 2. Methods Once the had been opened, a 4 F catheter tip pressure transducer (Gaeltec CTC/4F/USCI, Gaeltec Ltd, 2.1. Subjects Isle of Skye, UK) was introduced into the left ventricle with its tip located in the mid-portion of the cavity via the We studied 19 patients undergoing elective isolated aortic roof of the left and across the mitral valve [12,14]. valve replacement for predominant valvular Another similar 4 F catheter was introduced directly into the (16 patients) or regurgitation (3 patients), with a mean age with its tip at coronary ostial level as 67 ^ 12 (mean ^ SD) years; 9 patients were male. LV mass con®rmed on the echo image. Both signal outputs were index was 195 ^ 45g m22 measured by M-mode echocar- ®ltered with an upper cutoff frequency of 1 kHz, pre-ampli- diography using standard criteria [13]. Patients with clini- ®ed (Gaeltec S7b, Gaeltec Ltd), and transferred to two cally signi®cant ( . 50% of stenosis auxiliary lines of the echocardiograph. The pressure trans- in diameter) at prior coronary , or in whom ducer tipped catheters were calibrated electrically before the echocardiographic recordings were inadequate for analysis initial measurement at the same zero level. Zero pressure were not included. This study is a part of a clinical research was taken as atmospheric. The pulmonary artery wedge project approved by the Ethics Committee of the Royal pressure was used to identify the LV end-diastolic pressure. 326 X.Y. Jin et al. / European Journal of Cardio-thoracic Surgery 16 (1999) 324±330 city were determined by digitising the simultaneous M- modes of the left ventricle to derive cavity dimension and anterior wall thickness along with cavity pressure. Myocar- dial power was de®ned as the product of instantaneous circumferential wall stress and shortening velocity through- out systole. Myocardial stroke work was calculated as the time integral of instantaneous myocardial power during systole. Values of myocardial stroke work were indexed to a cubic centimetre of myocardium.

2.4. Statistical methods Fig. 2. Plots of ¯ow velocities of left anterior descending coronary artery versus pressure differences between the aorta and left ventricle during mid- Data are presented as mean ^ 1 standard deviation. Mini- Downloaded from https://academic.oup.com/ejcts/article/16/3/324/479982 by guest on 29 September 2021 later diastole with every 10 ms from a representative patient are shown. tab statistical software (PC Version, Release 8, 1991, Mini- Using linear regression analysis, the pre-operative (circles) and post-opera- tive (triangles) relationship of pressure differences (X) and ¯ow velocities tab Inc., USA) [16] was used for statistical analysis. Normal (Y) were: X ˆ 22:2 1 0:78Y (r ˆ 0:96) and X ˆ 21:7 1 0:88Y (r ˆ 0:95), distribution of data was checked using normal probability respectively. The major change of ¯ow velocity-pressure relation was a plots and was within 95% con®dence interval. Plots of signi®cant fall in pressure intercept (zero ¯ow pressure), from 22.2 coronary ¯ow velocity against pressure drop were analysed mmHg to 21.7 mmHg, while the proximal linear resistance showed little by linear regression. Paired t-tests were used to compare change. changes in these characteristics of coronary ¯ow-velocity 2.2.3. Measurement of LV dimension and wall thickness pattern before and after valve replacement. Unpaired t-tests M-mode echocardiogram of LV minor axis and anterior were performed to de®ne the difference between orthodox wall thickness was recorded with simultaneous cavity pres- linear resistance and proximal linear resistance, the differ- sure and electrocardiogram [12,14]. ence in LAD hemodynamics between the two cardioplegia Baseline measurements of coronary ¯ow velocity, pres- groups, expressed in absolute and percentage terms. sures and LV dimension were made before the cannulation Between-patient interrelations were examined by stepwise of cardiopulmonary bypass, and these were repeated at regression analysis. The reproducibility of measurements of immediately after weaning off cardiopulmonary bypass LAD ¯ow velocity and zero ¯ow pressure was assessed by (approximately 25±30 min reperfusion) prior to any require- inter-beat variation. This was ®rst examined by a paired t ment of inotropic drug was administrated. After the study, test of the values of two beats taken from same patient and the catheters were removed, and checked against an air- same study, and then the root mean square of the inter-beat operated dead-weight balance (Budenberg Gauge Co. Ltd, difference was expressed as the percentage of the mean, London, UK) [12,14]. representing the coef®ciency variation. P , 0:05 was taken as being statistically signi®cant. 2.3. Digitizing and calculations of coronary ¯ow velocities and hemodynamics 3. Results

We measured values of early, end, and mean diastolic 3.1. Patients aortic pressure, of early (minimum) and end diastolic LV pressure, and of LAD early (peak), end diastolic ¯ow velo- Age, gender and aortic valve disease (stenotic/regurgita- city. The time integral of LAD ¯ow velocity was computed tion: 8/2 vs. 8/1) did not differ between the groups, nor did and expressed in per beat and per minute. We also digitized the LV mass index (190 ^ 46 vs. 194 ^ 68, g m22)or aortic and LV diastolic pressures with simultaneous LAD intraoperative aortic cross clamp time (102^15 vs. ¯ow velocity. The orthodox LAD linear resistance was 97 ^ 16 min), all P . 0:05 (insigni®cant). The aortic calculated as the ratio of mean diastolic pressure difference valve was replaced with a bioprosthesis with a mean size between aorta and left ventricle to the mean diastolic LAD 25 ^ 2.4 mm. Normal performance of the bioprostheses was ¯ow velocity. We continuously plotted LAD ¯ow velocity con®rmed by transesophageal echocardiography post- against the pressure drop between aorta and left ventricle operatively. The mean cardiopulmonary bypass time was during diastole (Fig. 2). From these plots, we measured the 129 ^ 17 min. slope which de®nes LAD proximal linear resistance (mmHg 21 21 cm s ), and its intercept on the pressure axis, zero ¯ow 3.2. Changes in myocardial wall stress and stroke work pressure, in mmHg [6,7,15], and referenced to LV end- (Table 1) diastolic pressure. We have previously described methods of measuring There was a prompt fall in ventricular peak systolic stress myocardial stroke work in detail [12,14]. In brief, left after the operation, and a signi®cant fall in myocardial ventricular circumferential wall stress and shortening velo- stroke work. X.Y. Jin et al. / European Journal of Cardio-thoracic Surgery 16 (1999) 324±330 327

Table 1 Changes in LAD ¯ow velocity, aortic and left ventricular diastolic pressures after aortic valve replacement (mean ^ SD)a

Variable Before AVR (pre-bypass) 30 min after AVR P value

Heart rate (beats min21)74^ 11 98 ^ 19 0.001 Peak LV systolic wall stress (g cm22) 233 ^ 73 143 ^ 43 0.010 Myocardial stroke work (mJ cm23) 5.2 ^ 2.7 3.0 ^ 1.7 0.001 Peak aortic diastolic pressure (mmHg) 72 ^ 14.9 73 ^ 14.2 0.45 Mean aortic diastolic pressure (mmHg) 57 ^ 11.2 51 ^ 8.5 0.042 Fall in aortic pressure during diastole (mmHg) 16 ^ 8.8 22 ^ 11.8 0.029 LV end diastolic pressure (mmHg) 14 ^ 5.8 14 ^ 3.7 0.72 Early diastolic LAD ¯ow velocity (cm s21)56^ 22.8 85 ^ 23.0 0.0002 End diastolic LAD ¯ow velocity (cm s21)37^ 17.5 63 ^ 20.6 0.0004 LAD ¯ow velocity time integral per beat (cm) 20.3 ^ 6.7 28.3 ^ 9.3 0.0014 Downloaded from https://academic.oup.com/ejcts/article/16/3/324/479982 by guest on 29 September 2021 Orthodox LAD linear resistance (mmHg. cm21 s) 1.26 ^ 0.36 0.75 ^ 0.24 0.0001 Slope (proximal linear resistance) (mmHg. cm21 s) 0.56 ^ 0.27 0.46 ^ 0.24 0.21 Pressure axis intercept (LAD zero ¯ow pressure) (mmHg) 41 ^ 11.9 32 ^ 12.3 0.006 Pressure axis intercept above LV EDP (mmHg) 27 ^ 12.2 18 ^ 12.6 0.013

a AVR, aortic valve replacement; LAD, left anterior descending coronary artery; LV, left ventricle; EDP, end-diastolic pressure. P value by paired t-test.

3.3. LAD ¯ow velocity intercept remained approximately 40% of the mean value, the pressure intercept approached towards zero in individual Typical recordings of proximal LAD blood ¯ow velocity patients after operation. The comparison of LAD overall before and immediately after the operation are shown in Fig. linear resistance (by orthodox calculation) and the proximal 1. Peak LAD ¯ow velocities occurred during early diastole, linear resistance (by waterfall approach) also revealed that those during systole being considerably less, and often retro- the former was consistently greater both before operation grade in direction. Preoperatively, the peak diastolic blood (1.26 ^ 0.36 vs. 0.56 ^ 0.27, mmHg cm21 s, P , 0:001) 21 21 velocity had a mean value of 56 cm s , falling to 37 cm s , and afterwards (0.75 ^ 0.24 vs. 0.46 ^ 0.24, mmHg cm21 s, at end diastole. Thirty minutes after the reperfusion and P ˆ 0:006). weaning off cardiopulmonary bypass, both early diastolic and end diastolic ¯ow velocities were signi®cantly higher 3.6. Determinants of LAD ¯ow velocity than the corresponding values before, each by approxi- mately 20 cm s21. There was thus a signi®cant increase in Independent determinants of mean LAD diastolic ¯ow velocity time integral expressed as centimetre per beat velocity between patients were de®ned by stepwise regres- (Table 1). sion analysis, against mean aortic diastolic pressure, LAD proximal linear resistance, and pressure intercept (LAD zero 3.4. Coronary pressures ¯ow pressure), preoperatively and post-operatively. Before operation, aortic mean diastolic pressure, LAD linear resis- There was no signi®cant change in peak aortic diastolic tance and pressure intercept all proved to be independent pressure. Due to the fall of aortic diastolic pressure became determinants of ¯ow velocity in individual patients. In total, greater after the operation (from 16 mmHg to 22 mmHg), these three factors accounted for about 82% of the variance the mean aortic diastolic pressure fell by 6 mmHg corre- of mean LAD ¯ow velocity both before and after operation spondingly. Left ventricular minimum pressure pre-opera- (Table 2). There was no univariant linear correlation tively was 9 mmHg, increasing to 14 mmHg at end diastole. between left ventricular mass and any aspect of coronary These values were not consistently different 30 min after ¯ow velocity. operation (Table 1). 3.7. Effects of cardioplegia method 3.5. Interrelations between LAD ¯ow velocity and driving pressure (Table 1) Before operation, there was no statistically signi®cant difference between the patients who were to receive cold LAD overall linear resistance calculated in the orthodox or warm blood cardioplegia with regard to aortic and left way fell by more than 40% (P ˆ 0:0001) immediately after ventricular diastolic pressures, LAD ¯ow velocity, linear operation, but the slope of instantaneous LAD ¯ow velocity resistances, zero ¯ow pressure, or myocardial stroke work. against the difference between aortic and LV pressure did Following surgery, however, the percentage fall in zero ¯ow not change signi®cantly. Instead, their intercept on pressure pressure, with respect to LV end diastolic pressure, was axis fell in all patients from its mean value of 27 mmHg greater with warm, compared with cold, blood cardioplegia above left ventricular end diastolic pressure to 18 mmHg (P ˆ 0:012). Warm blood cardioplegia was also associated (P ˆ 0:013) after operation. As the standard deviation of the with a larger percentage increase in LAD ¯ow velocity time 328 X.Y. Jin et al. / European Journal of Cardio-thoracic Surgery 16 (1999) 324±330 integral (P ˆ 0:039) than cold blood cardioplegia. Peak use of vasodilators, such as adenosine, to slow the LAD ¯ow velocity, proximal and overall coronary resis- [7,9,17,18] would add a further complication. The mechan- tances, and myocardial peak wall stress and stroke work ism underlying the positive pressure intercept remains did not differ between the two groups (Table 3). uncertain. It has been explained in terms both of a vascular waterfall, and also a large intra myocardial capacitance with 3.8. Reproducibility a long time constant [15,17]. From practical point of view, therefore, we regard slope and intercept simply as poten- There was no consistent inter-beat difference in measur- tially independent descriptors of the observed linear relation ing LAD ¯ow velocity or zero ¯ow pressure when examined between diastolic ¯ow velocity and pressure. by paired t-test. The corresponding coef®ciencies of varia- tion were 5.7% and 4.0%, respectively. 4.1. Limitations of the study

This study has limitations. For obvious reasons, we did Downloaded from https://academic.oup.com/ejcts/article/16/3/324/479982 by guest on 29 September 2021 4. Discussion not investigate normal subjects, though all our patients had normal coronary arteriograms, and all were under general Flow velocities from proximal LAD have previously been anesthesia. We deliberately chose patients with aortic valve recorded using transesophageal echocardiography [8] and disease, since left ventricular hypertrophy provides an have been validated against invasive methods [9]. Since exacting test of myocardial preservation, and since the Bellamy's [6] ®rst proposal of using waterfall approach in unequivocal fall in regional myocardial work [12,14] with elucidating the hemodynamics of coronary vascular bed, operation allows the effect of loading to be clearly disso- similar LAD pressure-¯ow velocity interrelations in humans ciated from the increased coronary ¯ow velocity. We with normal have been recorded using avoided patients with coronary artery disease since the ¯ow velocity measurements derived by intra-coronary presence of regional stenosis, and subsequent bypass graft- Doppler [7]. In recent years, coronary pressure-¯ow velo- ing would have made the interpretation of proximal LAD city relationship has been applied to assess the effects of velocities problematic and since the effect of operation on coronary artery stenoses [17,18]. However, simultaneous ventricular loading in such patients would have been less high ®delity pressures in left ventricle and aorta have not decisive. Clinical investigation imposes constraints. The been recorded along with LAD ¯ow velocity in aortic valve number of patients studied was small, but the protocol disease or during aortic valve replacement, nor in previous was highly invasive, so we used the minimum to support studies of coronary ¯ow velocity pro®les observed weeks or our conclusions. The aortic pressure sensor had to be months after the valve replacement [10,11]. Our results removed before the was closed, so the study period demonstrate that immediately after correcting aortic steno- was correspondingly reduced. As with all Doppler measure- sis, blood ¯ow velocity is greatly increased in the proximal ments, ¯ow velocity rather than volume ¯ow was recorded, LAD, while regional myocardial wall stress and stroke work so we did not need to make assumption about ¯ow pro®le or have both fallen. In order to investigate the mechanism for arterial cross sectional area. Any changes in the ¯ow are this increase, we also recorded high ®delity aortic and LV likely to be in the same direction as those in ¯ow velocity pressures, so that instantaneous values of ¯ow velocity [19], therefore, when ¯ow velocity is zero in epicardial could be correlated with the corresponding pressure differ- vessels, so is volume ¯ow. Information about ¯ow velocities ence, representing driving pressure. In the range that we in more distal vessels would clearly have been of interest, measured, a linear relation between the two was demon- but this is beyond the capability of the methods we used. We strated (Fig. 2), but this relation was associated with a posi- de®ned driving pressure using left ventricular diastolic pres- tive pressure, with a mean value of 27 mmHg above LV sure as the base line to minimise the effects of variation in end-diastolic pressure, the zero ¯ow pressure. These ®nding the latter [20]. Using atmospheric pressure would not have are similar to previous studies involving pressure±¯ow rela- altered our conclusion. In order to determine the more tion [6,7], allowing for the difference between LV end physiological reference pressure however it would have diastolic and atmospheric pressure. The presence of such been necessary to study patients in whom heart rate was an intercept has been taken to imply that extrapolation slower, end-diastolic pressure higher, and proximal resis- beyond the measured range leads to ¯ow velocity falling tance lower than in the present study. to zero at ®nite driving pressure [6,7]. Blood ¯ow in the proximal LAD can thus be considered to behave resistively 4.2. Clinical implications in that there is a linear relation with pressure throughout diastole within the physiological range, whose slope de®nes Our results demonstrate that immediately after the termi- proximal linear resistance [15]. Direct demonstration that nation of cardiopulmonary bypass following aortic valve ¯ow does, in fact, fall to zero at the predicted pressure in replacement, blood ¯ow velocities are conspicuously the beating heart presents obvious dif®culties under clinical increased in the proximal LAD. This increase cannot be conditions; the long diastolic pause necessary for ¯ow to fall attributed to increased hemodynamic demand, since regio- might alter the properties of the micro circulation, while the nal work in the myocardium subtended by the LAD has X.Y. Jin et al. / European Journal of Cardio-thoracic Surgery 16 (1999) 324±330 329

Table 2 in classical overall coronary vascular resistance. However, Stepwise regression analysis of determinants of mean LAD diastolic ¯ow analysis in terms of instantaneous pressure-¯ow velocity velocity before and after aortic valve replacement (n ˆ 19) indicates that it is, in fact, mediated by a fall in the pressure Final step P value intercept. Paradoxically, proximal vascular resistance de®ned as the slope of the driving pressure-¯ow velocity Before aortic valve replacement relation remained unchanged. In contrast, inter-patient Constant (cm s21) 38.30 0.020 Slope: variance in pre- and postoperative ¯ow velocities depended (1) Aortic mean diastolic pressure 1.93 , 0.001 on perfusion pressure and proximal resistance and only (2) LAD proximal linear resistance 2 81 , 0.001 partially correlated to zero ¯ow pressure. We therefore (3) Pressure axis intercept 2 1.76 , 0.001 hypothesised that a fall in zero ¯ow pressure might be 21 Standard error (cm s ) 9.37 , 0.001 used as a marker of the disturbance caused by cardioplegia, R2 (%) 82.2 , 0.001 30 min after aortic valve replacement thus to distinguish it from other mechanisms accounting for Downloaded from https://academic.oup.com/ejcts/article/16/3/324/479982 by guest on 29 September 2021 Constant (cm s21) 100.47 , 0.001 the increase of proximal coronary ¯ow velocity. Slope: In order to test this idea, we investigated differences (1) Aortic mean diastolic pressure 1.17 , 0.001 between warm and cold blood cardioplegia, since we have (2) LAD proximal linear resistance 2 99 , 0.001 previously shown that in similar patients, departures from (3) Pressure axis intercept 2 1.71 , 0.001 Standard error (cm s21) 8.47 , 0.001 normal physiology were greater with the former [12]. In the R2 (%) 82.7 , 0.001 present study, it was apparent that with similar changes in myocardial loading and stroke work, the fall in zero ¯ow pressure was more than twice as greater with warm blood fallen, or to the effects of general anesthesia or inotropic cardioplegia, although the two cardioplegic regimes could drug administration. We believe, therefore, that it represents not be differentiated in terms of simple coronary linear resis- a direct effect of cardioplegia which leads to loss of the tance alone. The increase in ¯ow velocity time integral was normal balance between myocardial ¯ow and function also larger with warm blood cardioplegia, where it [21]. Such an increase occurring at effectively constant amounted to 130% of baseline, suggesting that it aortic perfusion pressure might well be attributed to a fall approached the value of coronary reserve previously

Table 3 Effects of cardioplegic methods on coronary hemodynamics during aortic valve replacement (mean ^ SD)

Variable Before AVR 30 min after AVR

CBPa WBP P value CBP WBP P value

Heart rate (beats/min) 74 ^ 12 75 ^ 11 0.91 92 ^ 19 103 ^ 17 0.19 Peak systolic wall stress 229 ^ 67 237 ^ 70 0.92 142 ^ 41 143 ^ 44 0.97 (g cm22) Myocardial stroke work 5.0 ^ 2.9 5.6 ^ 2.3 0.59 2.6 ^ 1.1 3.3 ^ 2.1 0.40 (mJ cm23) Mean aortic diastolic 66.7 ^ 13.1 62.9 ^ 12.3 0.53 58.9 ^ 6.2 64.9 ^ 12.2 0.20 pressure (mmHg) LV end diastolic pressure 12.8 ^ 7.2 12.1 ^ 7.8 0.86 11.2 ^ 3.8 15.5 ^ 7.2 0.12 (mmHg) Mean LAD diastolic ¯ow 49.1 ^ 22.8 39.6 ^ 10.2 0.25 68.1 ^ 23.3 70.8 ^ 17.2 0.77 velocity (cm s21) Orthodox linear 1.19 ^ 0.31 1.32 ^ 0.41 0.45 0.78 ^ 0.29 0.73 ^ 0.20 0.68 resistance (mmHg cm21 s) Proximal linear resistance 0.49 ^ 0.16 0.62 ^ 0.33 0.28 0.36 ^ 0.25 0.54 ^ 0.20 0.09 (mmHg cm21 s) Zero ¯ow velocity 32.1 ^ 11.9 26.2 ^ 8.7 0.22 26.0 ^ 11.1 12.3 ^ 5.9 0.003 pressure (above LVEDP) (mmHg) Percentage of fall in zero N/A N/A N/A 19 ^ 13 48 ^ 28 0.012 ¯ow pressure (%) LAD ¯ow velocity time 18.6 ^ 7.2 15.3 ^ 3.8 0.21 28.2 ^ 6.2 33.4 ^ 14.4 0.33 integral (VTI, m min21) Percentage of increase in N/A N/A N/A 53 ^ 59 127 ^ 81 0.039 LAD ¯ow VTI (%)

a CBP, cold blood cardioplegia; WBP, warm blood cardioplegia; N/A, not available. P value by two-sample t-test. 330 X.Y. Jin et al. / European Journal of Cardio-thoracic Surgery 16 (1999) 324±330 reported for hypertrophied myocardium [22]. Whether these Samuelson PN. Coronary and systemic vascular resistance during increases represent a mechanism of disease or simply a reperfusion and global myocardial ischaemia. Ann Thorac Surg marker of disturbed physiology, we have no de®nite 1988;46:447±454. [5] Hearse DJ, Maxwell L, Saldanha C, Gavin JB. The myocardial vascu- evidence. The patients we studied were selected to be at lature during ischaemia and reperfusion: a target for injury and protec- low risk, and there was thus no mortality or detectable tion. J Mol Cell Cardiol 1993;25:759±800. morbidity. However, we note that inappropriate coronary [6] Bellamy RF. Diastolic coronary artery pressure-¯ow relations in dog. vasodilatation induced by dipyridamole or adenosine in Circ Res 1978;43:92±101. the setting of myocardial perfusion imaging is a very [7] Dole WP, Richards KL, Hartley CJ, Alexander GM, Campbell AB, Bishop VS. Diastolic coronary artery pressure-¯ow velocity relation- predictable way of inducing regional in patients ships in conscious man. Cardiovasc Res 1984;18:548±554. with coronary artery disease [23]. [8] IIiceto S, Marangelli V, Memmola C, Rizzon P. Transesophageal Doppler echocardiography evaluation of coronary blood ¯ow velocity in baseline conditions and during dipyridamole-induced coronary

5. Conclusion vasodilatation. Circulation 1991;83:61±69. Downloaded from https://academic.oup.com/ejcts/article/16/3/324/479982 by guest on 29 September 2021 [9] Zehetgruber M, Porenta G, Mundigler G, et al. Transoesophageal Immediately after aortic valve replacement, ¯ow veloci- versus intra-coronary Doppler measurements for calculation of coron- ties are considerably increased in the proximal LAD coron- ary ¯ow reserve. Cardiovasc Res 1997;36:21±27. [10] Fujiwara T, Nogami A, Masaki H, Yamane H, Matsuoka S, Yoshida ary artery. This increase occurs in spite of a fall in regional H, Fukuda H, Katsumura T, Kajiya F. Coronary ¯ow velocity wave- myocardial work, and appears to represent a direct effect of forms in aortic stenosis and the effects of valve replacement. Ann cardioplegia. Analysis in terms of pressure-¯ow velocity Thorac Surg 1988;48:518±522. relations show that, unlike the variances in ¯ow velocity [11] Hongo M, Goto T, Watanabe N, Nakatsuka T, Tanaska M, Kinoshita occurring before or after operation, it is mediated by a fall O, Yamada H, Okubo S, Sekiguchi M. Relation of phasic coronary ¯ow velocity pro®le to clinical and hemodynamic characteristics of in zero ¯ow pressure. This fall is greater with warm blood patients with aortic valve disease. Circulation 1993;88:972±978. cardioplegia. Whether this greater departure from normality [12] Jin XY, Gibson DG, Pepper JR. Comparison of regional and global represents a detrimental effect of warm blood cardioplegia left ventricular function immediately after aortic valve replacement which we have previously shown to cause a less physiolo- using crystalloid, cold or warm blood cardioplegia. Circulation gical myocardial response than cold blood cardioplegia 1995;92(suppl II):II155±II162. 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