Influences of pravastatin and simvastatin, HMG-CoA reductase inhibitors, on myocardial stunning in dogs.
We examined the effects of pravastatin and simvastatin, HMG-CoA reductase inhibitors, on stunned myocardium in vivo. Pravastatin and simvastatin were given orally 2 mg/kg for 3 weeks. After 3 weeks of administration, pentobarbital-anesthetized dogs were subjected to 15-min left anterior descending (LAD) coronary artery occlusion followed by 2-h reperfusion. Myocardial segment function was determined by sonomicrometry. The tissue energy and carbohydrate metabolites were determined in the 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 reperfused myocardium as compared with control and pravastatin groups. The level of ATP in the simvastatin group was significantly lower as compared 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 ischemia.
Ichihara
K
K
Department of Pharmacology, Hokkaido College of Pharmacy, Otaru, Japan.
Satoh
K
K
Abiko
Y
Y
D000255:Adenosine Triphosphate / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D050260:Carbohydrate Metabolism; D002784:Cholesterol / Q000097:blood; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D017682:Myocardial Stunning / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology*; D019821:Simvastatin; D016277:Ventricular Function, Left / Q000187:drug effects
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000255:Adenosine Triphosphate; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin