Beneficial effects of a new carbacyclin derivative, ZK 36 374, in acute myocardial ischemia.

The potential therapeutic value of the chemically stable carbacyclin analog ZK 36 374 was studied in acute myocardial ischemia (MI). In anesthetized cats, the left anterior descending coronary artery was ligated and 30 min later an i.v. infusion of ZK 36 374 (0.18 microgram/kg X min) on vehicle was initiated and continued for 4.5 hr. ZK 36 374 reduced the ST-segment elevation at 2 to 5 hr (P less than .01) when compared to vehicle-treated MI cats. ZK 36 374 completely prevented the loss of CK specific activities and the decrease in percentage of bound cathepsin D in the infarcted area of the myocardium (P less than .01), but had no influences on any of these parameters in shamoperated animals. In addition, ZK 36 374 reversed the MI-induced decrease in circulating platelet count toward the preinfarction levels, probably by dispersion of circulating platelet aggregates. ZK 36 374 prevented the ischemia-induced loss of myocardial catecholamines from adrenergic nerve terminals. ZK 36 374, at 0.18 microgram/kg X min, exerted a maximum antiplatelet effect, whereas a significant decrease in arterial blood pressure was seen at 1.79 microgram/kg X min (-30-40%). This indicates a considerable dissociation between antiplatelet and blood pressure-lowering activities of ZK 36 374 in this model. The data demonstrate a significant protective effect of ZK 36 374 in acute MI that might be associated with its platelet-stabilizing, antiadrenergic and myocardial cytoprotective activities.