The object of this study was to determine whether high doses of insulin administered preventively in combination with glucose and potassium exert a protective effect upon the myocardium. This approach should result in a preoperative accumulation of the myocardial glycogen stores with an increased anaerobic provision of energy-rich substrates (ATP) during coronary ischemia. Two comparable groups of seven dogs each, undergoing experimental extracorporeal circulation (ECC) with 90-min aortic cross-clamping were examined. Cardiac output (CO), systolic left ventricular blood pressure (pventr), left ventricular enddiastolic pressure (LVEDP), mean central venous pressure (CVP), and heart rate (HR) were recorded at left atrial (LA) pressures of 5, 10, 15, and 20 mmHg in order to construct ventricular function curves. These data were registered prior to the onset of ECC (preischemic value), after termination of ECC and after two 10-min periods of reperfusion. The first group served as control and the second group received high iv doses of insulin (total 25 U/kg) within 60 min prior to the onset of the ECC. In the control group, pventrand CO after termination of the ECC and after the first reperfusion were significantly (P< 0.05) less than the preischemic values; after the second reperfusion they reached the preischemic range. In contrast, pventrand CO in the insulin group already were within the preischemic range at the termination of the ECC. After the first and the second reperfusion, CO was even greater than the preischemic value. LVEDP changed inversely, while CVP and HR showed no significant differences. The calculated left ventricular peak power (LVPpeak) changed proportional to the change in CO, and the systemic vascular resistance (SVR) did not show any significant change. It is concluded that preventive insulin administration helps maintain myocardial cell function during ischemia. By this method an earlier restitution of a vigorous cardiac performance can be achieved, indicating increased ischemic tolerance and improved myocardial protection.