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

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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 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. 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.