To date, ischemic preconditioning is regarded as the most powerful form of endogenous myocardial protection. For the purpose of surgical myocardial protection, a few clinical studies have investigated the effects of ischemic preconditioning in conjunction with hypothermia or blood cardioplegia during open heart surgery, but the results were controversial. We now tested the hypothesis that preconditioning improves myocardial protection in patients undergoing cold crystalloid cardioplegic arrest. 36 patients needing mitral prosthetic valve replacement for rheumatic heart disease were studied. Patients were evenly divided into two groups at random. Preconditioning was elicited by two cycles of 3 minutes ischemia by occlusion of vena cava and aortic cross-clamping followed by 2 minutes reperfusion under cardiopulmonary bypass. All hearts were arrested using 4 degrees C St. Thomas' Hospital solution before the intracardiac operative program. Myocardial protective effects were mainly assessed by electrocardiac activities, leakage of myocardial enzymes, myocardial contractility, and early postoperative recovery. The results indicated that there was a significant reduction of ST-segment shifting (ST-segment elevation, 0.07 +/- 0.02 vs 0.22 +/- 0.07 mV, p < 0.05, at 4 hours post reperfusion) and smaller release of creatine kinase-MB (87 +/- 11.5 vs 143 +/- 17.2 IU/L, p < 0.05, at 12 hours post reperfusion) in the preconditioning group. Preconditioning also enhanced myocardial contractility (dp/dtmax = 1490 +/- 75 vs 1280 +/- 88 mmHg/sec, at 30 minutes post reperfusion, p < 0.05) and promoted early postoperative recovery. The present study suggests that ischemic preconditioning reduces ischemia-reperfusion injury in human hearts even when combined with cold crystalloid cardioplegia.