Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction

OBJECTIVES We tested to find out whether pravastatin restores the infarct s ize (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5'- nucleotidase which plays a key role in the IF-induced cardioprotection. BACKGROUND The IS-limiting effect of IF is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotec tive effects. METHODS Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured a fter 30 min occlusion and 3 h reperfusion of circumflex coronary artery wit h or without the IP procedure (5 min occlusion and 10 min reperfusion). Add itionally, ecto-5'-nucleotidase activities of ischemic and nonischemic myoc ardium were measured immediately after IP procedure. RESULTS This dose of pravastatin did not normalize the increased level of s erum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 3 6.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4% , p < 0.001). Pravastatin treatment did not affect IS or the effect of IP u nder normocholesterolemia. The activation of ecto-5'-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in n ormocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.0 5) and restored by pravastatin treatment (2.9-fold). CONCLUSIONS Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IF and IF-induced ecto-5'-nucleotidase a ctivation, which were both blunted by hypercholesterolemia. The activation of ecto-5'-nucleotidase may be worth further investigation as a possible me chanism for the hypercholesterolemia-induced retardation and pravastatin-me diated restoration of the cardioprotective effect of IP. (C) 1999 by the Am erican College of Cardiology.