Experimental evaluation of myocardial protective effect of prostacyclin analog (OP-41483) as an adjunct to cardioplegic solution

Abstract

A stable prostacyclin analog (OP-41483) was evaluated for myocardial protective effect against global ischemia with the use of cardioplegia. Isolated canine hearts (n = 25) were exposed to 60 minutes of warm (37 degrees C) global ischemia after the arrest by crystalloid cardioplegia. Prostaglandin analog was given in three different ways: preadministration (700 ng/kg body weight per minute) before ischemia for 30 minutes (group I, n = 5), given as a component of cardioplegic solution (600 ng/ml, group II, n, = 6), and post-administration (25 ng/kg body weight per minute) during reperfusion for 30 minutes (group III, n = 7). During reperfusion, coronary sinus blood flow, 6-keto-prostaglandin F1 alpha in coronary sinus blood, and myocardial oxygen consumption were measured during reperfusion. As a result, groups II and III showed significantly better global left ventricular function (developed pressure, maximum dP/dt, and diastolic compliance) than the control group (without prostaglandin analog, n = 7) and group I. Myocardial oxygen consumption at reperfusion (1 minute) was significantly larger in group II than in the control group. 6-keto-prostaglandin F1 alpha flux was significantly larger in group II than in the other three groups during reperfusion. The results indicated that prostaglandin analog has a beneficial effect on myocardial protection under global ischemia with cardioplegia, particularly when used as a component of cardioplegic solution and also during reperfusion. The mechanism may relate to the cytoprotective effect (including protection of endothelium with enhanced endogenous prostacyclin production at reperfusion and also to the modulation of reperfusion per se.