Prostacyclin (PGI2) and some of its major breakdown products (6-keto-PGFi,6-keto-PGEi, and 13,14-dihydro 6,15-diketo-PGFia) were studied in an isolated perfused cat heart preparation during myocardial ischemia. At an infusion rate of 10 ng/g heart weight per minute, PGI2and the related compounds caused no changes in perfusion pressure, contractile force (CF), the first derivative of the contractile force (dF/dt), and heart rate in control hearts perfused at coronary flows of 20-35 ml/min. Induction of global ischemia by perfusion at 0.6 to 0.7 ml/min for 120 minutes resulted in a significant release of creatine kinase (CK) activity and compounds having a free amino-nitrogen group into the perfusate. Ischemic hearts exhibited an increase in resting tension of 2.3 ± 0.2 g, mean ± SEM. Upon reperfusion, untreated ischemic hearts showed a partial restoration of mechanical performance, CF = 43 ± 5%, and dF/dt = 40 ± 5% of control. PGI2infusion inhibited the ischemic-induced CK release and the increase in perfusate amino-nitrogen concentration. Resting tension also remained low (i.e., 0.8 ± 0.1 g). Recovery of CF and dF/dt upon reperfusion was significantly higher (86 ± 8% and 88 ± 10%, respectively) than in the untreated ischemia group. Myocardial CK activity was significantly higher in PGI2-infused hearts (35.8 ± 2.6 IU/mg protein) compared to those infused with its vehicle (26.3 ± 2.8,P< 0.01).'Breakdown products of PGI2only slightly protected against ischemia. PGI2is beneficial in myocardial ischemia in vitro, even without its well known action preventing platelet aggregation and independent of its induction of coronary vasodilation.CircRes 47: 757-763, 1980