CARDIOPROTECTION IN CARDIAC-SURGERY WITH PROPHYLACTIC INFUSION OF NIFEDIPINE OR NITROGLYCERINE BEFORE CARDIOPULMONARY BYPASS - STUDIES WITHTROPONIN-T AS PARAMETER FOR PERIOPERATIVE MYOCARDIAL DAMAGE

The present study was designed to test if prophylactic intravenous nif edipine or nitroglycerine could reduce myocardial damage after cardiop ulmonary bypass. 45 patients scheduled for elective coronary artery by pass grafting were divided at random into three groups: Group 1: contr ol; group 2: nifedipine (0.25 mug/kg/min); group 3: nitroglycerine (1. 5 mug/kg/min). Infusion period reached from the beginning of anaesthes ia until crossclamp of the aorta. Myocardial damage was estimated by t roponin T (TnT), CK-MB and ST-segment analysis of the ECG. TnT is a ca rdiospecific protein from the contractile apparatus of striated muscle cells. TnT-levels might provide a very sensitive marker of small amou nts of cardiac muscle necrosis. It was tested with an ELISA/one-step s andwich-assay with streptavidin-technology [9]. Criteria for ischemia in the ST-segment analysis were (according to Smith et al. [191): ST-d epression > 1 mm from baseline or ST-elevation > 2 mm from baseline at J-point + 60 ms. Statistical interpretation was done by one- and two- factorial analyses of variance (including multivariate analyses of var iance). Correlation between two variables was tested by regression ana lysis. A level of p < 0.05 was taken for indicating statistical signif icance. Biometrical data, circulation data and data from cardiopulmona ry bypass were without significant differences among all groups (Table s 1 and 2). Starting from normal values (< 0.05 ng/ml) TnT significant ly rose in all groups immediately after cardiopulmonary bypass and rem ained elevated until the forth day after operation (values between 0.4 and 0.6 mug/ml) (Figure 1). Elevation was significantly (p < 0.05) lo wer after cardiopulmonary bypass and at the end of operation in the ni fedipine than in the control- or nitroglycerine-group. No differences were seen between the groups at later investigation points. A signific ant correlation existed between duration of ischemia and maximal TnT-l evels in the control-(r = 0.58; p < 0.05) (Figure 2), but neither in t he nifedipinenor in the nitroglycerine-group. In all groups CK-MB leve ls steeply rose after cardiopulmonary bypass (p < 0.01), reaching a ma ximum at end of operation and slowly returning to baseline values unti l the forth postoperative day (Figure 3). Seven patients had higher ma ximal TnT-values than the other (>1.5 mug/l), three of them had in par alles elevated CK-MB values, two of them signs of ischemia on the ECG (at least at one measurement point). Changes in the ECG or elevated CK -MB-levels without increased TnT-levels have not been seen. Catecholam ines for a short period were necessary for two patients in each group. No connection between catecholamine need and TnT-levels could be reco gnized. Two intracellular compartments of TnT can be differentiated: A n unbound cytosolic troponin T pool and structurally bound constituent s. The unbound cytosolic part is early released when membranes are dam aged. It seems to correspond to the early rise of TnT-levels after car diopulmonary bypass. Nifedipine may be able to reduce this reversible, probably ischemia- or reperfusion-related cell damage. Because of the serum half-life of TnT (two to three hours) elevated TnT-values from the first to the forth postoperative day indicate irreversible cell de struction. Nifedipine has no influence on the extend of the cell necro sis, which may be due to direct mechanical trauma during operation. In conclusion, the study demonstrates the efficiency of prophylactic nif edipine before cardiopulmonary bypass in reduction of early myocardial damage after cardiopulmonary bypass.