Prevention of myocardial enzyme release by ranolazine in a primate model of ischaemia with reperfusion

Abstract

In control anaesthetized baboons subjected to 30 min occlusion of the left anterior descending coronary artery, followed by 5.5 h reperfusion, total plasma levels for creatine kinase (CK) and lactate dehydrogenase (LDH) were markedly elevated in a time-related manner. In a second group of baboons pretreated 10 min prior to ischaemia with ranolazine [(+/-)-N-(2,6-dimethyl-phenyl)-4[2-hydroxy-3-(2-methoxyphenoxy)propyl]-1 - piperazine acetamide dihydrochloride; RS-43285-193] at 500 micrograms kg-1 i.v., followed by continuous infusion of 50 micrograms kg-1 min-1, neither enzyme was significantly elevated at any time point. Similarly, serum levels of the cardiospecific isoenzyme CK2 were 8 fold greater in the controls than in the ranolazine-treated animals at 6 h. The results indicate that ranolazine pretreatment abolished cardiac enzyme release over a 5.5 h reperfusion period, indicating a potential protective effect.