INFLUENCES OF PRAVASTATIN AND SIMVASTATIN, HMG-COA REDUCTASE INHIBITORS, ON MYOCARDIAL STUNNING IN DOGS

We examined the effects of pravastatin and simvastatin, HMG-CoA reduct ase inhibitors, on stunned myocardium in vivo. Pravastatin and simvast atin were given orally 2 mg/kg for 3 weeks. After 3 weeks of administr ation, pentobarbital-anesthetized dogs were subjected to 15-min left a nterior descending (LAD) coronary artery occlusion followed by 2-h rep erfusion. Myocardial segment function was determined by sonomicrometry . The tissue energy and carbohydrate metabolites were determined in th e 2-h-reperfused hearts. Administration of pravastatin and simvastatin for 3 weeks decreased serum cholesterol level and blood pressure (BP) . Simvastatin resulted in a worsening of segment shortening in the rep erfused myocardium as compared with control and pravastatin groups. Th e level of ATP in the simvastatin group was significantly lower as com pared with that in the control group. The other metabolite levels were not significantly altered by either pravastatin or simvastatin. These results suggest that simvastatin enhances stunning of the myocardium in association with ATP reduction after reperfusion subsequent to isch emia.