Prevention of myocardial enzyme release by ranolazine in a primate model of ischaemia 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 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.
Allely
M C
MC
Department of Pharmacology, Syntex Research Centre, Riccarton, Edinburgh.
Alps
B J
BJ
D000083:Acetanilides; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003327:Coronary Disease / Q000201:enzymology*; D003402:Creatine Kinase / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology*; D010215:Papio; D010879:Piperazines / Q000494:pharmacology*; D000069458:Ranolazine
D000083:Acetanilides; D002317:Cardiovascular Agents; D010879:Piperazines; D000069458:Ranolazine; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase