Concentration-dependent effects of prostacyclin on the response of the isolated guinea pig heart to ischemia and reperfusion: possible involvement of the slow inward current.

Isolated guinea pig hearts were subjected to 40 min of low flow global ischemia followed by 30 min of reperfusion. The effects of prostacyclin (PGI2) (10 pg/ml-10 ng/ml) on the response of hearts to ischemia and reperfusion were studied. Ischemia caused a 55% decline in contractile force and the development of contracture. Sinus bradycardia and varying degrees of atrioventricular conduction block were observed. Reperfusion was associated with rapid recovery of contractile force and a gradual decline in resting tension. PGI2 (1 ng/ml) enhanced ischemic contracture significantly at 10 and 20 min (P less than .05). Hearts made ischemic in the presence of PGI2 developed higher degrees of atrioventricular conduction block when compared to controls. Reperfusion in the presence of 1 or 10 ng/ml of PGI2 caused a significant decline in recovery of force (P less than .05) and enhanced reperfusion-associated contracture. We examined the influence of verapamil (100 ng/ml) and lowering external calcium to 1.25 mM on hearts subjected to ischemia and reperfusion in the absence of presence of PGI2 (1 ng/ml). Neither verapamil nor 1.25 mM calcium exerted significant effects on the decline of contractile force during ischemia or on recovery of contractility upon reperfusion. However, verapamil did reverse the reperfusion-associated cardiodepressant effects of PGI2. Verapamil abolished contracture in control hearts after 5 and 10 min of reperfusion and prevented the enhancement of contracture in hearts reperfused in the presence of PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)