Role of prostacyclin in the preservation of ischemic myocardial tissue in the perfused cat heart.

Prostacyclin (PGI 2 ) and some of its major breakdown products (6-keto-PGFi,,, 6-keto-PGEi, and 13,14-dihydro 6,15-diketo-PGFi a ) were studied in an isolated perfused cat heart preparation during myocardial ischemia.At an infusion rate of 10 ng/g heart weight per minute, PGI 2 and 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.PGI 2 infusion 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 PGI 2 -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 PGI 2 only slightly protected against ischemia.PGI 2 is 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