BENEFICIAL-EFFECTS OF A NEW CARBACYCLIN DERIVATIVE, ZK-36-374, IN ACUTE MYOCARDIAL ISCHEMIA

  • 1 January 1981
    • journal article
    • research article
    • Vol. 219  (1) , 243-249
Abstract
The potential therapeutic value of the chemically stable carbacyclin analog ZK 36374 [5-[(E)-(1S,5S,6R,7R)-7-hydroxy-6-[(E)-(3S,4RS)-3-hydroxy-4-methyloct-1-en-6-ynyl]bicyclo[3.3.0]octan-3-yliden]-pentanoic acid] was studied in acute myocardial ischemic (MI). In anesthetized cats, the left anterior descending coronary artery was ligated and 30 min later an i.v. infusion of ZK 36374 (0.18 .mu.g/kg .times. min) on vehicle was initiated and continued for 4.5 h. ZK 36374 reduced the ST-segment elevation at 2-5 h (P < 0.01) when compared to vehicle-treated MI cats. ZK 36374 completely prevented the loss of CK [creatine kinase] specific activities and the decrease in percentage of bound cathepsin D in the infarcted area of the myocardium (P < 0.01), but had no influence on any of these parameters in sham-operated animals. In addition, ZK 36374 reversed the MI-induced decrease in circulating platelet count toward the preinfarction levels, probably by dispersion of circulating platelet aggregates. ZK 36374 prevented the ischemia-induced loss of myocardial catecholamines from adrenergic nerve terminals. ZK 36374, at 0.18 .mu.g/kg .times. min, exerted a maximum anti-platelet effect, while a significant decrease in arterial blood pressure was seen at 1.79 .mu.g/kg .times. min (-30-40%). This indicates a considerable dissociation between antiplatelet and blood pressure-lowering activities of ZK 36374 in this model. Apparently there is a significant protective effect of ZK 36374 in acute MI that might be associated with its platelet-stabilizing, antiadrenergic and myocardial cytoprotective activities.