PREVENTION OF MYOCARDIAL ENZYME-RELEASE BY RANOLAZINE IN A PRIMATE MODEL OF ISCHEMIA WITH REPERFUSION

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 μg kg-1 i.v., followed by continuous infusion of 50 μg kg-1 min-1, neither enzyme was significantly elevated at any time point. Similarity, 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.