Since its introduction by Salerno and colleagues [1]

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1 Randomized Trial of Intermittent Antegrade Warm Blood Versus Cold Crystalloid Cardioplegia Luc M. Jacquet, MD, Philippe H. Noirhomme, MD, Michel J. Van Dyck, MD, Gebrin A. El Khoury, MD, Amin J. Matta, MD, Martin J. Goenen, MD, and Robert A. Dion, MD Cardio-thoracic Intensive Care Unit, Department of Cardio-thoracic and Vascular Surgery, and Department of Cardiac Anesthesia, University Hospital Saint Luc, Brussels, Belgium Background. We performed a prospective randomized trial to compare intermittent antegrade warm blood cardioplegia with intermittent antegrade and retrograde cold crystalloid cardioplegia. Methods. Two hundred consecutive patients scheduled for isolated coronary bypass surgical procedures were randomized into two groups: Group 1 (n 92) received cold crystalloid cardioplegia with moderate systemic hypothermia, group 2 (n 108) received intermittent antegrade warm blood cardioplegia with systemic normothermia. Preoperative, intraoperative, and postoperative data were prospectively collected. Results. For the same median number of distal anastomoses, cardiopulmonary bypass duration and total ischemic arrest duration ( versus minutes, p < 0.001) were shorter in group 2 than in group 1. Apart from a higher right atrial pressure in the cold cardioplegia group, no hemodynamic difference was observed. Aspartate aminotransferase, creatine kinase-mb fraction, and cardiac troponin I levels were significantly lower in group 2 than in group 1. Outcome variables were not significantly different. Conclusions. Intermittent antegrade warm blood cardioplegia results in less myocardial cell damage than cold crystalloid cardioplegia, as assessed by the release of cardiac-specific markers. This beneficial effect has only marginal clinical consequences. Normothermic bypass has no deleterious effect on end-organ function. (Ann Thorac Surg 1999;67:471 7) 1999 by The Society of Thoracic Surgeons Since its introduction by Salerno and colleagues [1] and Lichtenstein and associates [2], continuous warm blood cardioplegia has been routinely used by a growing number of surgeons. Both in vitro and in vivo studies have demonstrated the superiority of continuous warm blood cardioplegia over conventional cold cardioplegia with regard to myocardial metabolic and functional recovery [3, 4]. A major limitation is the flooding of cardioplegia in the operating field, which could hinder the surgeon. Interruption of the infusion is thus frequently necessary for technical reasons and is reported to have no deleterious effect on cardiac recovery, provided that the time off cardioplegia does not exceed 13 minutes [5]. Deliberate use of intermittent antegrade warm blood cardioplegia (IAWBC) has been proposed as a safe and reliable technique of myocardial protection, as reported by Calafiore and associates in a historical comparative study [6]. Body temperature during cardiopulmonary bypass (CPB) is another controversial issue [7, 8]. Indeed, hypothermia decreases end-organ oxygen consumption and offers some degree of protection during periods of low flow or low perfusion pressure, but it also has side effects (ie, on the coagulation cascade) [9]. Tissue protection Accepted for publication July 11, Address reprint requests to Dr Jacquet, Intensive Care Unit, University Hospital Saint-Luc, 10 Ave Hippocrate, 1200 Brussels, Belgium. during normothermia has also been questioned, especially cerebral protection, because some studies have reported a higher incidence of neurologic events [7]. Our study was initiated to evaluate, in a prospective randomized trial, the effect of IAWBC on myocardial protection and that of normothermic bypass on endorgan function compared with our previous usual practice of intermittent antegrade and retrograde cold crystalloid cardioplegia with moderate hypothermia. Patients and Methods With approval of the institutional ethics committee, 200 consecutive patients scheduled for isolated coronary bypass surgical procedures between December 1995 and November 1996 gave their informed written consent to participate in the study. Patients undergoing emergent procedures or combined valvular and coronary surgical procedures, as well as those with a carotid stenosis greater than 80% were excluded from the study. Eligible patients were randomized into two groups: Group 1 (n 92) received combined antegrade and retrograde cold crystalloid cardioplegia with moderate systemic hypothermia; group 2 (n 108) received intermittent antegrade normothermic blood cardioplegia with systemic normothermia. Anesthesia was induced with sufentanil (3 g/kg body weight) and midazolam (0.05 mg/kg) and maintained by a continuous administration of sufentanil 1999 by The Society of Thoracic Surgeons /99/$20.00 Published by Elsevier Science Inc PII S (98)

2 472 JACQUET ET AL Ann Thorac Surg RANDOMIZED TRIAL OF INTERMITTENT WARM CARDIOPLEGIA 1999;67:471 7 Table 1. Composition and Rate of Administration of Normothermic Hyperkalemic Cardioplegia a Cardioplegia Normothermic blood (ml/min) KCl (2 meq/ml) (ml/h) Duration (min) 1st 300 Bolus 2 ml, then 150 ml 2 2nd rd th th a Normothermic blood is derived from the bypass circuit and is infused in the aortic root through a separate line. The rate of infusion is regulated by a dedicated roller pump. The hyperkalemic solution is added in this separate line by means of a syringe pump. (1 to 1.5 g kg 1 h 1 ) and propofol (0.1 to 0.25 mg kg 1 h 1 ). Muscle paralysis was obtained with pancuronium (0.1 mg/kg). All patients received tranexamic acid (10 mg/kg) as a bolus at induction followed by a continuous infusion of 1 mg kg 1 h 1 during CPB. Cardiopulmonary bypass was instituted with a heparin-coated circuit (Duraflo II; Baxter, Irvine, CA) and a heparincoated hollow fiber membrane oxygenator (Spiragold; Baxter). The circuit was primed with 1.5 L of plasmalyte and 2 ml/kg of 15% mannitol. Systemic heparin was given to achieve an activated clotting time greater than 450 seconds ( 300 U/kg). In group 1, cardiac arrest was obtained by infusion of 500 ml of cold crystalloid solution (1,000 ml Hartman, 14 meq KCl, 8 meq NaHCO 3,25 meq MgSO 4, procaine 200 mg) into the aortic root, combined with 500 ml of the same solution infused in the coronary sinus at a pressure of 40 mm Hg or lower. An additional 500-mL solution without procaine was administered every 60 minutes or whenever necessary (eg, at resumption of electrical activity). Body temperature was allowed to decrease to a minimal temperature of 30 C. Rewarming was initiated during completion of the last distal anastomosis. In group 2, cardiac arrest was achieved by intermittent infusion of normothermic hyperkalemic blood in the aortic root. Blood was collected from the oxygenator and infused into the aortic root using a roller pump. The tubing was connected to a syringe pump containing a solution of 2 meq K /ml. The composition and rate of administration are presented in Table 1. The time elapsed between two infusions, which defines an ischemic arrest period, never exceeded 15 minutes. During CPB, blood temperature was maintained around 37 C. In the intensive care unit (ICU), heart rate and rhythm, systemic blood pressures, and pulmonary artery pressures were continuously monitored. A complete hemodynamic profile, including cardiac output determination (mean of three thermodilution measurements after random injection of 10 ml of 5% glucose at room temperature) and arteriovenous oxygen content difference, was systematically obtained on arrival from the operating room, at 4 and 8 hours postoperatively, on days 1 and 2 after operation, and whenever deemed clinically necessary. Derived variables were calculated using standard formulas. A 12-lead electrocardiogram was recorded at the same time points for detection of ischemic episodes or Q-wave infarction, or both. Additional recordings were performed if clinically necessary. Blood was drawn for protein and ion determination and for enzymatic assay (creatine kinase [CK] and aspartate aminotransferase) simultaneously. For CK-MB mass measurement and for cardiac troponin I (ctni) dosage, blood was immediately centrifuged and frozen for later determination. The CK-MB mass was measured using a fluorometric enzyme assay and ctni using a specific enzyme-linked immunosorbent assay (Stratus, Dade, Miami, FL). The area under the curve for these marker levels was calculated by a linear trapezoidal rule. In the ICU, anesthesia was systematically maintained until the sixth postoperative hour with a continuous infusion of sufentanil (0.5 g kg 1 h 1 ). A propofol infusion was adapted for sedation (0.5 to 2 mg kg 1 h 1 ) until patients were ready for extubation. Intravenous paracetamol (2 g) or piritramide (2 to 4 mg) was administrated for analgesia. Extubation was performed as soon as the patients were able to maintain adequate gas exchange with a pressure support at5cmh 2 O above positive end-expiratory pressure and a respiratory rate less than 20 breaths per minute and if they were hemodynamically stable, adequately rewarmed, and not bleeding. Colloids (gelatine or hydroxyethylstarch) were infused if pulmonary artery occlusion pressure was less than 15 mm Hg and if one of the following criteria was not met: mean blood pressure greater than 65 mm Hg, heart rate less than 110 beats per minute, cardiac index greater than 2.5 L min 1 m 2, or urine output less than Table 2. Preoperative Characteristics a Variable Group 1 (cold cardioplegia) (n 92) Group 2 (warm cardioplegia) (n 108) p Value Age (y) Male/female 63/29 82/ Body surface area (m 2 ) Previous MI Diabetes Renal insufficiency Hypertension COPD LVEF (%) No. of diseased vessels 3 (2 3) 3 (2 3) 0.65 Semiurgent procedure Preoperative treatment Beta-blockers Calcium antagonists ACE inhibitors Intravenous heparin a Data presented are mean value standard deviation, median (interquantile range), or number of patients. ACE angiotensin-converting enzyme; COPD chronic obstructive pulmonary disease; LVEF left ventricular ejection fraction; MI myocardial infarction.

3 Ann Thorac Surg JACQUET ET AL 1999;67:471 7 RANDOMIZED TRIAL OF INTERMITTENT WARM CARDIOPLEGIA ml kg 1 h 1. If these values were not reached after volume loading, inotropic or vasoactive drugs, or both, were administered according to the hemodynamic data. Homologous red blood cells were given for a hemoglobin level greater than 8.5 to 9 g/100 ml. Fresh-frozen plasma, cryoprecipitate, or platelets were given only to hemorrhagic patients presenting with abnormal hemostasis. Patients were usually discharged from the ICU on the second posterative day and left the hospital 1 week later. For between-group comparisons, unpaired t tests or Mann-Whitney U tests were performed according to the distribution for continuous variables and the Mann- Whitney U test for discrete variables. For comparison of serially recorded variables, an analysis of variance for repeated measures was used. If a difference was found, a t test was performed for pairwise comparisons. Proportions in the two groups were compared using the 2 test. Differences were considered statistically significant at a p value less than Table 3. Intraoperative ata a Variable Group 1 (n 92) Group 2 (n 108) p Value Total distal 4 (3 5) 4 (3 5) 0.63 anastomoses Patients with LIMA graft Patients with RIMA graft Patients with bilateral IMA graft Patients with GEA graft Volume of 1, cardioplegic solution (ml) CPB duration (min) Aortic cross-clamp duration (min) Total ischemic arrest duration (min) Mean blood pressure (mm Hg) Vasoconstrictors during bypass Lowest body temperature ( C) Weaning of bypass Ventricular fibrillation External pacing IABP Inotropic drugs a Data presented are mean value standard deviation, median (interquantile range), or number of patients. CPB cardiopulmonary bypass; GEA gastroepiploic artery; IABP intraaortic bypass pump; IMA internal mammary artery; LIMA left internal mammary artery; RIMA right internal mammary artery. Table 4. General Outcome a Variable Results Group 1 (n 92) Group 2 (n 108) p Value Deaths Reoperation for bleeding Q-wave infarction Prolonged ischemia Renal insufficiency Acute dialysis Pulmonary insufficiency Stroke Stay in ICU (h) 46 ( ) 45.5 (42 48) 0.95 Stay in hospital (days) 9 (7 10) 9 (7 10) 0.79 a Data presented are median (interquartile range) or number of patients. ICU intensive care unit. The preoperative characteristics of the two groups are presented in Table 2. Both groups were similar, except for semiurgent procedures (patients requiring intravenous nitroglycerin for relieve of their anginal symptoms), which were more frequent in group 2. Table 3 summarizes the intraoperative data. For the same median number of distal anastomoses, total ischemic arrest and CPB duration were shorter in group 2. Mean blood pressure during CPB was significantly lower in group 2, and more patients in this group required vasopressors to maintain their mean blood pressure at greater than 50 mm Hg. Ventricular fibrillation after aortic cross-clamp release was significantly more frequent in the cold cardioplegia group. The general outcome variables, especially number of new Q-wave myocardial infarctions, duration of ICU stay, and number of deaths were not different between the two groups (Table 4). Two deaths in group 1 were related to low cardiac output and one to cerebral infarction. In group 2, two deaths were also due to a low output state, and one was a sudden death on postoperative day 15. The incidence of stroke was also similar in both groups. Hemodynamic data are summarized in Figure 1. Right atrial pressure was statistically significantly higher in group 1 than in group 2 at 4 hours ( versus mm Hg, p 0.016) and at 8 hours after operation ( versus mm Hg, p 0.006). All other measured and calculated variables were not different at any time point. To be taken off bypass, 24% of patients in group 1 and 23% in group 2 required inotropic support ( p 0.77). No difference in inotropic requirement appeared during the postoperative evolution. Intraaortic balloon support was necessary in 3 patients in each group ( p 0.8). Arterial oxygen content was similar in both groups, but mixed venous oxygen content was significantly lower in group 1 at 4 hours after operation ( versus ml O 2 /100 ml, p ). The calculated oxygen consumption index was significantly higher in group 1 at 4 hours after operation

4 474 JACQUET ET AL Ann Thorac Surg RANDOMIZED TRIAL OF INTERMITTENT WARM CARDIOPLEGIA 1999;67:471 7 Fig 1. Comparison of hemodynamic data between the two study groups: (A) cardiac output, (B) mean pulmonary artery pressure, (C) central venous pressure, and (D) right ventricular stroke work index (R.V.S.W.I.). Open bars indicate cold cardioplegia; solid bars indicate normothermic cardioplegia. (T-1 induction of anesthesia; T0 arrival in intensive care unit; T1 4 hours after operation; T2 8 hours after operation; T3 postoperative day 1; T4 postoperative day 2; * p 0.05.) ( versus ml O 2 min 1 m 2, p 0.016) but not later on. The evolution of myocardial enzymatic release is presented in Figure 2. Aspartate aminotransferase; CK-MB mass, and ctni were significantly lower in group 2 than in group 1 at each time point, except on day 2 after operation. When patients treated by electrical countershock (Fig 3) were withdrawn from analysis, the same significant difference between the groups was observed. The peak level of ctni was lower in the normothermic group ( versus g/l, p ), as was the mean area under the curve calculated until the second postoperative day ( versus g h 1 L 1, p 0.001) (Fig 4). Neither gas exchanges (assessed by the ratio of partial pressure of oxygen to fraction of inspired oxygen) nor mechanical properties of the lungs (assessed by the pseudostatic compliance) were different. Duration of intubation was also unaffected by the type of cardioplegia (median, 17 hours [interquartile range, 14 to 20 hours] in group 1; median, 17 hours [interquartile range 14 to 20 hours] in group 2, p 0.9). Total chest tube drainage was 835 ml in group 1 and 792 ml in group 2 ( p 0.47). Homologous blood transfusion was also identical in both groups (median, 509 ml in group 1 versus 538 ml in group 2, p 0.58). As presented in Figure 5, total fluid balance (including cardioplegic solution) during the first 48 hours was higher in group 1 than in group 2 at all time points. Finally, among the biologic data, higher K levels were noted in group 2 patients at on arrival from the operating room ( versus , p 0.046). All other measured data were not different at any time point; in particular, hemoglobin and platelets levels were the same on postoperative day 2. Comment The deliberate use of IAWBC was first reported by Calafiore and colleagues [6] in a retrospective study comparing 250 patients operated on with this technique with their last 250 patients operated on with cold blood cardioplegia. They reported less inotropic support requirement, less CK-MB release, and a shorter stay in the ICU using IAWBC. A prospective, randomized study comparing IAWBC with cold blood cardioplegia by Pel-

5 Ann Thorac Surg JACQUET ET AL 1999;67:471 7 RANDOMIZED TRIAL OF INTERMITTENT WARM CARDIOPLEGIA 475 Fig 3. Comparison of cardiac troponin I (ctn-i) levels in patients without electrical countershock. (* p 0.05; ** p 0.01; other abbreviations as in Fig 1.) Fig 2. Comparison of markers of cardiac cell damage in the two study groups: (A) aspartate aminotransferase (ASAT); (B) creatine kinase-mb mass assay (CK-MB); (C) cardiac troponin I. (* p 0.05; ** p 0.01; other abbreviations as in Fig 1. letier and associates [10] also showed less release of CK-MB and troponin T in the IAWBC group. Because interruption of cardioplegia is synonymous with warm ischemia and is thus believed to be harmful, these surprising results were challenged by in vitro studies. If some studies seemed to indicate poor metabolic and functional recovery when warm blood cardioplegia was interrupted for 10 minutes [11, 12], more recent studies in isolated pig or rabbit hearts suggest that no negative effect on the myocardium is observed after an interruption of up to 10 minutes [13, 14]. Encouraged by these early clinical and laboratory results, we decided to compare IAWBC with our routine practice of cold crystalloid cardioplegia administered by a combined antegrade and retrograde route, acknowledging that the route of administration is different and could influence the results. Our study demonstrates a significant reduction of myocardial cell damage with the use of IAWBC. Specific markers of cardiac cell lesions, especially ctni, are indeed significantly lower after normothermic cardioplegia at each time point until the second postoperative day. Even if we exclude patients requiring electrical shock for ventricular fibrillation, the difference remains highly significant. The mean peak value and the mean area under ctni curves until postoperative day 2 were also significantly different, indicating that different rates of myocardial release cannot explain the observed disparity in blood levels. A dilutional factor can also be excluded because hematocrit and protein levels are the same in both groups. Because ctni has been shown to be highly specific for myocardial cell damage and to be unaffected by skeletal muscle lesions or renal insufficiency [15, 16], this finding clearly indicates that fewer myocardial cell lesions occurred in the normothermic group. However, few consequences, if any, were observed in the postoperative hemodynamic profiles. Right atrial pressure in the cold cardioplegia group at 4 hours after operation and at postoperative day 1 was higher, but pulmonary artery pressure and right ventricular stroke work index were not statistically different, suggesting Fig 4. Comparison of mean area under cardiac troponin I (ctn-i) curve until day 2 after operation.

6 476 JACQUET ET AL Ann Thorac Surg RANDOMIZED TRIAL OF INTERMITTENT WARM CARDIOPLEGIA 1999;67:471 7 Fig 5. Comparison of cumulative fluid balance until postoperative day 2. (O.R. in the operating room; * p 0.01; other abbreviations as in Fig 1.) that higher filling pressures were required in the cold group to maintain right ventricular function. Moreover, the proportion of patients requiring inotropic support or an intraaortic balloon pump was the same in both groups. A higher proportion of our patients required inotropic support than those evaluated by Lichtenstein and colleagues [5] and Calafiore and associates [6]. Both more liberal criteria for the use of inotropic drugs and longer total ischemic duration in our normothermic groups (57 minutes of a cross-clamping time of 69 minutes) can explain this difference between the present study and previous reports. If, as suspected, longer intraoperative ischemia increases the need for inotropic support, this assumption certainly raises some concern as to the outcome of patients with a lower ejection fraction and deserves further investigation. However, even if the ischemic duration was relatively long in our study, ctni release was lower in the normothermic group and inotropic requirements for normothermia and cold cardioplegia were the same. In accordance with previous studies, the incidence of ventricular fibrillation after cross-clamp release was significantly lower in the normothermic cardioplegia group. The incidence of ventricular or supraventricular arrhythmias and the need for temporary pacing were not different at any time until patient discharge from the hospital. During bypass, significantly more patients in the normothermic group required vasoconstrictors to maintain their mean blood pressure above 50 mm Hg, but this requirement seems not to be associated with any side effect, especially with respect to mammary artery flow and the incidence of ischemic episodes. Although more patients in the normothermic group were treated with angiotensin-converting enzyme inhibitors, neither angiotensin-converting enzyme inhibitors nor calcium entry blockers were associated with an increased need for vasoconstrictors. Total fluid balance was higher in the cold cardioplegia group. The use of hyperkalemic patient blood infused through a side arm of the CPB arterial line obviates the need for infusing extra fluid to obtain cardioplegic arrest in the normothermic group. At the end of operation, and despite increased diuresis, the cold cardioplegia group had a total fluid balance 700 ml higher, and this difference was still 800 ml on the second postoperative day. With regard to lung function variables, and as reported by Birdi and colleagues [17], no difference was noted in gas exchange and ventilation variables. We were also unable to show any difference in bleeding rate or blood product requirement, even after correction for body surface area and despite the well-known deleterious effect of cold temperature on hemostasis and platelet function [18]. This finding may be related to our systematic use of tranexamic acid and perhaps our use of heparin-coated circuits, which could have lowered the incidence of bleeding in the cold cardioplegia group [19, 20]. Moreover, hypothermia during bypass was moderate (mean lowest temperature, 31.4 C), with probably a moderate effect on hemostasis, which could explain the differences between our study and others [9]. A further concern, when using normothermic bypass, was neurologic outcome [7 10]. Our incidence of stroke was the same in both groups, but the number of patients in our study was too small to be conclusive because the incidence of this complication was low. It must be emphasized that glycemia was not a concern with our low cardioplegia volume and that mean blood pressure during bypass was maintained above 45 to 50 mm Hg. Even though the design of the present study was to maintain true normothermia in our patients during bypass, the actual lower temperature drifted below 35 C on average. This relatively small change in body temperature could have some protective effects on the central nervous system. Finally, length of stay in the ICU and in the hospital were the same in both groups. However, these are very gross and nonspecific markers of outcome because they are influenced by numerous external factors independent of the cardioplegia or bypass temperature. For instance, because no stepdown unit is available in our hospital, patients were usually maintained in the ICU until the second postoperative day. In conclusion, IAWBC results in less myocardial cell damage than cold crystalloid cardioplegia, as assessed by the release of cardiac-specific markers. Better right ventricular preservation is possible but does not result in less need for inotropic support. Normothermic bypass increases the need for vasoconstrictors during CPB without significant effects on end-organ function. However, the possibility of early extubation has to be addressed with another study design, and neurologic outcome has to be evaluated in a larger population. References 1. Salerno TA, Houk JP, Borrozo CAM, et al. Retrograde continuous warm blood cardioplegia: a new concept in myocardial protection. Ann Thorac Surg 1991;51: Lichtenstein SV, Ashe KA, El Dalati H, Cusimano RJ, Panos A, Slutsky AS. Warm heart surgery. J Thorac Cardiovasc Surg 1991;101: Menasché P, Peynet J, Touchot B. Normothermic cardiople-

7 Ann Thorac Surg JACQUET ET AL 1999;67:471 7 RANDOMIZED TRIAL OF INTERMITTENT WARM CARDIOPLEGIA 477 gia: is aortic cross-clamping still synonymous with myocardial ischemia? Ann Thorac Surg 1992;54: Yau TM, Ikonomidis JS, Weisel RD. Ventricular function after normothermic versus hypothermic cardioplegia. J Thorac Cardiovasc Surg 1993;105: Lichtenstein SV, Naylor CD, Feindel CM, et al. Intermittent warm blood cardioplegia. Circulation 1995;92 (Suppl II):II Calafiore AM, Teodori G, Mezzetti A, et al. Intermittent antegrade warm blood cardioplegia. Ann Thorac Surg 1995; 59: Martin TD, Craver JM, Gott JP, et al. Prospective, randomized trial of retrograde warm blood cardioplegia: myocardial benefit and neurologic threat. Ann Thorac Surg 1994;57: Birdi I, Regragui I, Izzat MB, Bryan AJ, Angelini G. Influence of normothermic systemic perfusion during coronary artery bypass operations: a randomized prospective study. J Thorac Cardiovas Surg 1997;114: Tönz M, Mihaljevic T, von Segesser K, et al. Normothermia versus hypothermia during cardiopulmonary bypass: a randomized, controlled trial. Ann Thorac Surg 1995;59: Pelletier LC, Carrier M, Leclerc Y, Cartier R, Wesolowska E, Solymoss C. Intermittent antegrade warm versus cold blood cardioplegia: a prospective, randomized study. Ann Thorac Surg 1994;58: Ko W, Zelano J, Fahey AL, Berman K, Isom OW, Krieger RH. Ischemic tolerance of the arrested heart during warm cardioplegia. Eur J Cardiothorac Surg 1993;7: Landymore RW, Marble AE, Fris J. Effect of intermittent delivery of warm blood cardioplegia on myocardial recovery. Ann Thorac Surg 1994;57: Tian G, Xiang B, Butler KW. A 31 P magnetic resonance study of intermittent warm blood cardioplegia. J Thorac Cardiovasc Surg 1995;109: Torracca L, Pasini E, Curello S, et al. Continuous versus intermittent warm blood cardioplegia: functional and energetics changes. Ann Thorac Surg 1996;62: Adams JE III, Bodor GS, Davila-Roman VG, et al. Cardiac troponin I. A marker with high specificity for cardiac injury. Circulation 1993;88: Bhayana V, Gougoulias T, Cohoe S, Henderson AR. Discordance between results for serum troponin T and troponin I in renal disease. Clin Chem 1995;41: Birdi I, Regragui IA, Izzat MB. Effects of cardiopulmonary bypass temperature on pulmonary gas exchange after coronary artery operation. Ann Thorac Surg 1996;61: Boldt J, Knothe C, Welters I, Dapper FL, Hempelmann G. Normothermic versus hypothermic cardiopulmonary bypass: do changes in coagulation differ? Ann Thorac Surg 1996;62: Gu YJ, van Oeveren W, Akkerman C, Boonstra PW, Huyzen RJ, Wildevuur CRH. Heparin-coated circuits reduce the inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1993;55: Pugh SC, Wielogarski AK. A comparison of the effects of tranexamic acid and low-dose aprotinin on blood loss and homologous blood usage in patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth 1995;9: Kennedy School Sabbatical The Thoracic Surgery Foundation for Research and Education announces that applications for a year-long sabbatical to do graduate studies in health care policy at Harvard University s Kennedy School of Government are now available. Candidates will be accepted early on a rolling admission basis by the graduate school, and scholarships will be awarded by The Foundation s Education Committee. The Kennedy School will review completed applications for the Program starting January 1, 1999, and is prepared to make decisions on applications within 2 weeks of their receipt. The Foundation will make a decision on an application for Alley-Sheridan Scholarships within 2 weeks of its receipt to The Foundation office. If an interested surgeon has applied to The Kennedy School very early in January, it is possible to have the admissions and scholarship decisions completed by February 1. Please call Lainie Castle at The Foundation office for more information at (312) , extension by The Society of Thoracic Surgeons Ann Thorac Surg 1999;67: /99/$20.00 Published by Elsevier Science Inc