The aim of our study was to investigate the contribution of the adrenocorticotropic hormone fragment, ACTH (4-10), on the recovery of postischemic cardiac function. Effects of ACTH (4-10) on caspase-3 activity, cardiomyocyte and endothelial apoptosis, and HO-1 protein expression were studied. Rats were treated with various doses of ACTH (4-10), and then 12 h later, anesthetized, hearts were isolated, perfused, and subjected to 30-min ischemia followed by 120-min reperfusion. Cardiac function including heart rate, coronary flow, aortic flow, and left ventricular developed pressure were recorded. After 120-min reperfusion, 200 mug/kg of ACTH (4-10) significantly improved the recovery of aortic flow, coronary flow, and left ventricular developed pressure from their untreated control values of 15.3 +/- 0.9 ml/min, 6.5 +/- 0.9 ml/min, and 10 +/- 0.6 kPa to 20.7 +/- 1.3 ml/min, 24.8 +/- 1.8 ml/min and 13.7 +/- 0.7 kPa, respectively. Heart rate did not show significant changes during reperfusion. ACTH (4-10) treatment resulted in a reduction in infarct size, caspase 3 activity, apoptosis, and an increase in HO-1 expression. When ACTH (4-10) was given at the moment of reperfusion, the drug failed to improve the postischemic recovery of the myocardium. Thus, ACTH (4-10) can be a useful tool for the prevention of the development of ischemia/reperfusion-induced injury.