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Ann Thorac Surg 1996;61:128-134
© 1996 The Society of Thoracic Surgeons
Divisions of Cardiovascular Surgery, Sunnybrook Health Science Centre, and the Toronto Hospital, University of Toronto, Toronto, Ontario, Canada
Accepted for publication September 2, 1995.
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Abstract |
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Methods. To assess the effects of cardioplegia on right ventricular protection, 52 patients undergoing isolated bypass grafting were randomized to intermittent warm or cold blood cardioplegia. The two groups were similar with respect to age, sex, ventricular function, and right coronary stenoses. Cross-clamp times were similar (warm, 64 ± 22 minutes; cold, 63 ± 15 minutes; not significant). The cumulative time of cardioplegia interruption was longer in the cold group (42 ± 8 minutes) than in the warm group (31 ± 14 minutes; p < 0.002). A rapid-response thermodilution catheter was employed to assess postoperative right ventricular ejection fraction and end-diastolic and end-systolic volume indices.
Results. The right ventricular ejection fraction was greater in the warm group at 6 hours (warm, 0.46 ± 0.06; cold, 0.37 ± 0.08; p < 0.05) and 8 hours (warm, 0.43 ± 0.08; cold, 0.37 ± 0.08; p < 0.05) postoperatively. The right ventricular end-diastolic volume index was less in the warm group 8 hours postoperatively (warm, 83 ± 11 mL/m2; cold, 94 ± 16 mL/m2; p < 0.05). There were no differences in pulmonary arterial pressures or right ventricular stroke work index.
Conclusions. Despite intermittent normothermic ischemia of half the cross-clamp time, patients receiving warm cardioplegia maintained right ventricular hemodynamics after bypass grafting.
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Introduction |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Transient right ventricular (RV) dysfunction has been previously documented after coronary artery bypass grafting despite myocardial protection with intermittent antegrade cold blood cardioplegia [1, 2]. Right ventricular protection during bypass operations may not be optimal when traditional intermittent cold blood cardioplegia is employed. We have previously demonstrated that the RV free wall rewarms quickly after being cooled with hypothermic cardioplegia [1]. This occurs due to the anterior position of the RV, its proximity to operating room lights and the ambient temperature, the rewarming from adjacent right atrial blood, and coronary and noncoronary collateral flow [3, 4]. Even when the RV is adequately cooled, cold cardioplegia may not allow adequate O2 transfer to tissues. Delivery of cardioplegia distal to right coronary artery stenoses may be further limited by the increased viscosity of cold blood solutions [2, 5]. Inhomogeneous distribution of cardioplegic solution may predispose the heart to ischemic damage [1, 2].
Continuous antegrade infusion of warm blood cardioplegia has been heralded as a theoretical improvement over cold blood cardioplegia, postulating that ischemia is avoided and reperfusion damage limited [6]. Warm blood cardioplegia allows adequate O2 transfer to tissues, and may be better distributed distal to stenoses because it is less viscous than cold blood. Continuous infusion of antegrade warm blood cardioplegia may therefore promote better protection of the RV than intermittent cold blood cardioplegia.
However, inadequate visualization of the operative field with continuously infused cardioplegia has necessitated interruption of flow during construction of distal anastomoses. In this center, the technique of continuous antegrade warm blood cardioplegia has therefore been modified to an intermittent warm blood cardioplegia technique. The intermittent infusion of warm blood cardioplegia renders the RV intermittently ischemic. The consequence of intermittent normothermic RV ischemia on postoperative RV function is unknown. This prospective, randomized trial was therefore undertaken to determine the influence of intermittent cold or warm cardioplegia on postoperative RV hemodynamics.
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Material and Methods |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Surgical and Cardioplegia Techniques
Technical details concerning warm and cold blood cardioplegia techniques have been documented extensively in previous communications [6–8]. Single right atrial and ascending aortic cannulation were employed for cardiopulmonary bypass. An ascending aortic cardioplegia cannula was inserted for cardioplegia delivery and venting during the operation. Systemic oxygenation and perfusion during cardiopulmonary bypass was accomplished with membrane oxygenators, nonpulsatile flows of 2.4 L•min-1•m-2 (to maintain mean arterial pressure >50 mm Hg), moderate hemodilution (20% to 25%), and alpha-stat acid-base balance. Systemic temperatures of those patients randomized to the warm group were maintained between 35° and 37°C. Patients randomized to the cold group were actively cooled to systemic temperatures of 25° to 30°C.
The composition of 4:1 blood cardioplegia has been described in detail previously [7, 8]. Blood cardioplegia was infused at 37°C for the warm group and 5° to 8°C for the cold group; otherwise, the cardioplegia delivery technique and conduct of operation were identical for both groups. High-potassium blood cardioplegia (1,000 mL) was administered into the aortic root at 200 to 300 mL/min once the aortic cross-clamp was applied. Thereafter, low-potassium blood cardioplegia was infused continuously at 100 to 150 mL/min in both groups, with interruption of cardioplegia delivery only during construction of the distal anastomoses. Once the coronary artery was incised and opened, cardioplegia delivery was temporarily stopped in both groups, and the cardioplegia cannula was used as a vent to improve visualization of the anastomosis. After completion of the distal anastomoses, a 500-mL bolus of warm or cold cardioplegia was delivered at 200 to 300 mL/min, after which the rate was again reduced to 100 to 150 mL/min. In both groups, cardioplegia was also infused intermittently through each completed vein graft using a manifold system. Immediately before removal of the aortic cross-clamp, patients in both the warm and cold groups received a terminal infusion of 350 mL of warm (37°C) blood cardioplegia over 2 minutes. Proximal anastomoses were performed after aortic declamping using a partial occlusion clamp.
Measurements
The ischemic time was measured for each patient. Ischemic time was defined as the cumulative time during which cardioplegia was stopped for construction of distal anastomoses. The longest ischemic interval was defined as the longest period of time between doses of cardioplegia. Ventricular function was monitored with the insertion of an RV rapid response, thermodilution REF-1 catheter (Baxter Healthcare Corp, Edwards Critical Care Division, Santa Ana, CA). Hemodynamic measurements (in triplicate) included RV ejection fraction, cardiac output, RV and pulmonary artery pressures, and right atrial and pulmonary capillary wedge pressures. Systemic pressures were measured through a radial arterial line. Calculated indices of ventricular function included RV end-diastolic and end-systolic volume indices, RV stroke work index, and systemic and pulmonary vascular resistance according to standard formulas.
Hemodynamic measurements were made once catheters were inserted (after induction of anesthesia) and at 2, 4, 6, 8, 12, and 24 hours after cross-clamp removal. Measurements were performed under stable hemodynamic conditions. Hemodynamic equilibrium was considered to be established when pressure measurements varied less than 5% and when patients were adequately anesthetized and volume loaded early after operation. Measurements were not performed or included in the analysis if patients required inotropes or afterload-reducing agents, or if patients were shivering or tachycardic despite adequate anesthesia and muscle relaxation. The number of patients in the warm and cold groups, respectively, who met one or more of the these criteria were as follows: 2 hours, 1 and 6; 4 hours, 6 and 5; 6 hours, 7 and 9; 8 hours, 6 and 7; 12 hours; 2 and 2; and 24 hours, 7 and 6. Patients remained intubated, paralyzed, anesthetized, and ventilated during measurements performed in the first 12 hours postoperatively. Serial blood samples for creatine kinase-MB isoenzyme assay were obtained at 0, 4, 8, 12, 20, and 28 hours after patient arrival in the intensive care unit.
Statistical Analysis
Patient demographics and intraoperative and postoperative outcomes were compared between the two cardioplegia groups by unpaired t test or Mann-Whitney rank-sum test, as appropriate, for continuous data, and by 
2 test for categoric data. A two-way analysis of variance was used to assess differences in serial postoperative hemodynamics between the two cardioplegia techniques, with differences specified by Scheffé's test. A correlation analysis (Pearson correlation analysis) was used to evaluate the relation between right and left ventricular stroke work indices.
A p value less than 0.05 was considered significant. Categoric data are displayed as absolute numbers or percentages. Continuous data are depicted as the mean and standard error of the mean for graphs or as the mean and standard deviation of the mean for tabular formats.
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Results |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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. There were no significant differences in clinical characteristics between the two groups. Significant (greater than 50% stenosis) narrowing of the right coronary artery was present equally in both groups.
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lists perioperative data. Cross-clamp time and cardiopulmonary bypass time were similar with cold or warm cardioplegia. During the cross-clamp period, cardioplegia was interrupted during construction of distal anastomoses for both warm and cold techniques. The cumulative time during which no cardioplegia was infused in each patient was defined as the ischemic time. The ischemic time was significantly larger for patients receiving intermittent cold cardioplegia. The longest interval between doses of cardioplegia was also significantly longer in patients receiving intermittent cold cardioplegia. The peak postoperative creatine kinase-MB release was less for patients in the warm group. The total volume of fluids (albumin, crystalloid solutions, blood, blood products) during the first 12 hours postoperatively did not differ between groups (warm, 1,256 ± 659 mL; cold, 1,048 ± 401 mL).
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depicts the serial postoperative hemodynamic data for cold and warm groups. There were no statistically significant differences in systemic pressures, stroke volume indices, or vascular resistance measurements. Systolic and mean pulmonary artery pressures were similar in both groups. Pulmonary vascular resistance was lower in the warm group at 4, 6, and 12 hours. There was no correlation between RV and left ventricular stroke work index for either group in our study (Pearson correlation coefficient: warm, r = 0.29; cold, r = 0.16).
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illustrates RV ejection fraction and RV end-systolic and end-diastolic volume indices. After cold cardioplegia, the RV ejection fraction decreased significantly from baseline in the postoperative period (p = 0.01), and remained significantly lower 24 hours after operation. After warm cardioplegia, there was a small increase in RV ejection fraction postoperatively (p = 0.04). The RV ejection fraction in the warm group was significantly higher than in the cold group at 6 and 8 hours postoperatively (p = 0.05).
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Comment |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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The use of continuous antegrade warm blood cardioplegia may obviate the need for RV cooling. Continuous oxygen delivery to myocardial tissues during the cross-clamp period has been proposed as a method of reducing ischemia and hence reperfusion damage [6]. Clear evidence, however, has demonstrated inhomogeneous delivery of cardioplegia even in the absence of coronary artery occlusions [13]. Furthermore, high pressure and high flow of blood through an arteriotomy during coronary artery bypass grafting may prevent adequate visualization. At this institution cardioplegia is completely stopped during construction of the distal anastomosis, and is restarted immediately after completion of the anastomosis. This prospective, randomized trial was therefore undertaken to determine the effect of interrupting cardioplegia delivery on postoperative RV function.
Right Ventricular Function
The RV is a ``volume pump'' and highly dependent on preload conditions. The low compliance characteristics of the RV invalidate the use of filling pressures as an adequate guide to ventricular size [14]. To assess RV function, volume estimates are necessary. Assessment of RV function is difficult. A perfectly precise and accurate technique does not exist. Radionuclide ventriculography and echocardiography only provide estimates of RV volumes and ejection fraction. Many investigators have employed rapid-response thermodilution catheters to provide estimates of RV function [14–18]. Rapid-response thermodilution catheters may allow for estimates of RV function. The catheter consists of a fast-response (100 ms) thermistor and intracardiac electrodes, and allows for beat-to-beat analysis of the time-temperature curve. Thermodilution-derived RV ejection fraction has been correlated to biplane angiographic [15] and nuclear ventriculographic derived ejection fractions [16]. Although not ideal, measurements are reproducible (absolute differences within each set of three measurements is not significant), and changes in response to hemodynamic alterations are proportional [15] (r = 0.86), thus allowing for comparison between groups.
Right Ventricular Function and Temperature
Boldt and colleagues [9] employed antegrade cold crystalloid cardioplegia in patients undergoing coronary bypass grafting, and discovered RV temperatures were 15.1° ± 1.8°C in patients without right coronary artery stenoses and 22.2° ± 2.1°C in those with right coronary artery stenoses. They employed rapid-response thermodilution catheters in patients with right coronary stenoses, and observed that RV ejection fractions decreased from 0.44 ± 0.03 preoperatively to 0.34 ± 0.01 postoperatively. Right ventricular end-diastolic volume and end-systolic volume indices increased by 38% and 70%, respectively. Right ventricular temperatures during the operation strongly correlated with the changes in RV ejection fraction and volumes. They concluded that impairment of postoperative RV function was directly related to warmer RV temperatures. Myocardial temperatures were not measured in either group in the present study. Perhaps myocardial temperatures decreased towards room temperature in the warm group, and increased to the ambient temperature in the cold group.
Perhaps RV myocardial temperatures are not as important as previously believed. Bert and Singh [18] studied 32 patients with right coronary artery stenosis undergoing isolated coronary bypass grafting. Patients were randomized to hypothermic and normothermic cardiopulmonary bypass. They demonstrated significantly warmer right ventricular temperatures with normothermic bypass (24° ± 2°C) than hypothermic bypass (17° ± 1°C; p < 0.05). Thermodilution RV ejection fraction and RV volumes were similar in both groups postoperatively.
In the present study we also demonstrated normal RV hemodynamics in patients receiving warm cardioplegia. Delivery of usable oxygen in the areas subserved by stenosed right coronary arteries may have been higher in the warm group because of the better rheology of less viscous warm blood. However, the ischemic time and longest ischemic interval were longer in the cold group, because all surgeons felt more confident with the luxury of hypothermia and performed additional tasks (such as suturing left internal mammary artery pedicles to epicardium or repairing leaks) before restarting the cardioplegia. Furthermore, cold cardioplegia was interrupted immediately after an arteriotomy nick, whereas warm cardioplegia was stopped only after the surgeon and assistant were set up and ready to begin suturing the anastomoses. Differences in cold and warm ischemic times may have contributed to the differences observed in this study.
In both the warm and cold groups, 5 patients with right coronary artery stenoses less than 50% did not receive bypass grafts. In the rest of the patients, saphenous vein bypass grafts were constructed either to the right coronary artery or to one of the ongoing branches. The influence of proximal versus distal stenoses, the extent of right coronary atherosclerosis, and the order in which grafts were performed to the right coronary circulation were not addressed in this study and may also have influenced outcomes. Continued perfusion of the microcirculation with noncoronary collateral flow during the time cardioplegia is stopped could also account for maintained RV hemodynamics after intermittent warm blood cardioplegia. Collateral flow during periods of cardioplegia interruption empirically appears to be greater among patients receiving warm cardioplegia [8, 19].
Collateral flow may be influenced by the vasodilation and lower systemic vascular resistance associated with normothermic bypass [8, 20]. Low vascular resistance results in high bypass flow rates and infusion of vasoconstrictors, which may increase noncoronary collateral flow. Vasodilation associated with normothermic cardiopulmonary bypass persists postoperatively and results in high cardiac outputs [8, 20]. A decrease in RV afterload secondary to pulmonary vasodilation may also explain RV hemodynamics in the warm group. Although systolic pulmonary artery pressures were similar in both groups, pulmonary vascular resistance was lower at 4, 6, and 12 hours postoperatively in the warm group.
Differences in RV function may be related to differences in left ventricular function. Yau and associates [21] studied 53 patients undergoing isolated coronary artery bypass grafting. They randomized patients to intermittent antegrade warm or antegrade cold cardioplegia. They demonstrated that left ventricular end-systolic elastance and preload recruitable stroke work index were increased after warm cardioplegia. They attributed the increased left ventricular systolic function to either improved myocardial protection, elevated arterial lactate concentrations, or increased circulating catecholamine levels. Improved left ventricular function after warm cardioplegia could result in better septal wall motion and thus improve RV function passively.
Patients randomized to the warm cardioplegia group had a significantly lower RV ejection fraction at baseline (preoperatively). This may be attributed either to differences in preoperative loading conditions or to inadequate randomization.
Intermittent Cardioplegia
In this study, no attempts were made at local control of blood flow at the arteriotomy site. Methods of improving visualization during coronary anastomoses include techniques such as irrigation of the field with saline solution or air, proximal and distal clamping or snaring of arteries, intracoronary probe insertion, and lowering cardioplegia or cardiopulmonary bypass flow rates. These techniques, however, are cumbersome, prolong the operating time, may lead to complications, and are frequently ineffective. Furthermore, normothermic electromechanical arrest of the heart reduces myocardial oxygen consumption to levels comparable with those found with hypothermia [22]. However, it is believed that even short periods of interruption of warm cardioplegia can lead to irreversible cell death and permanent regional ventricular dysfunction [23–25]. Surgeons were therefore more expeditious when constructing anastomoses in the warm group, which accounts for the shorter ischemic intervals.
In this prospective, randomized study, we demonstrated that despite periods of normothermic ischemia totaling half the cross-clamp time, patients receiving intermittent warm blood cardioplegia maintained normal RV hemodynamics postoperatively. However, preservation of normal hemodynamics in the postoperative period cannot by itself be introduced as evidence of adequate myocardial preservation. With inhomogeneous delivery or interruption of cardioplegia, the RV subendocardium may be vulnerable to ischemia [13]. The resultant patchy nature of subendocardial necrosis [26] may go undetected with global measurements of ventricular function such as RV ejection fraction [27]. Therefore, preserved ventricular function after coronary bypass grafting does not exclude limited regional myocardial damage. Clearer evidence of improved myocardial protection may have been demonstrated in this study by obtaining RV muscle biopsy specimens for adenine nucleotide assays. Further studies are necessary to identify accurately the safe period of normothermic cardioplegic interruption, if such a period exists.
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Acknowledgments |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Footnotes |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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