Adenosine methylene diphosphate (AMPCP), a 5'-nucleotidase inhibitor, was evaluated as an adjunct to cold crystalloid cardioplegic myocardial protection. Cardiopulmonary bypass (CPB) was instituted at 28 degrees C in two groups of mongrel dogs (each, n = 6). Myocardial ischemia was induced for 150 min by aortic cross clamping. Crystalloid cardioplegia (4 degrees C) was infused into the aortic root at 15 ml/kg/20 min in the control group (CP). The experimental group (CP + AMPCP) received identical doses of cardioplegia supplemented with 250 microM AMPCP. While on CPB, the mean arterial pressure was 70 mm Hg and the myocardial temperature ranged from 16 to 22 degrees C. Hemodynamic parameters were recorded prior to institution of CPB and at 15 and 45 min following the termination of CPB. Starling curves were constructed for cardiac index (CI), mean arterial pressure (MAP), mean left ventricular pressure (LVP), +dP/dt and -dP/dt at each time point for left atrial pressures between 5 and 12.5 mm Hg. The area under each curve was calculated and expressed as a percentage of prebypass values. Statistical analysis was performed with Student's two-tailed t test. The data demonstrate that although recovery of CI, MAP, heart rate, and LVP was similar in both groups, statistically significant improvement in recovery of myocardial compliance (-dP/dt) and systolic function (+dP/dt) was seen with AMPCP. The addition of the 5'-nucleotidase inhibitor, AMPCP, to cold crystalloid cardioplegia enhances postischemic myocardial performance in vivo and may be useful during prolonged periods of global myocardial ischemia.