Title
Lipophilic HMG-CoA
reductase inhibitors increase myocardial stunning in dogs.
Source
Journal of Cardiovascular Pharmacology. 35(2):256-62, 2000 Feb.
Abstract
Pretreatment of dogs with simvastatin, a lipophilic
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
reductase inhibitor, increases myocardial contractile
dysfunction during reperfusion after ischemia (stunning), with reduction of
tissue adenosine triphosphate (ATP). This was thought to be a consequence of
prevention of ubiquinone biosynthesis by the lipophilic
inhibitor in the myocardial cell. We examined whether other
lipophilic HMG-CoA
reductase inhibitors also influence myocardial stunning in
dogs. Vehicle, atorvastatin (2 mg/ kg/day), fluvastatin (4 mg/kg/day), or
cerivastatin (40 microg/kg/ day) was orally administered for 3 weeks.
Hydrophilic pravastatin (4 mg/kg/day) also was given. After 3 weeks,
pentobarbital-anesthetized dogs were subjected to 15-min left anterior
descending coronary artery occlusion followed by 2-h reperfusion. Myocardial
segment function was determined by sonomicrometry. Tissue levels of ATP were
determined in 2-h reperfused hearts. All inhibitors significantly decreased
serum cholesterol level. The three lipophilic inhibitors
resulted in a worsening of segment function in the reperfused myocardium, as
compared with the vehicle group. The levels of ATP in the atorvastatin,
fluvastatin, and cerivastatin groups were significantly lower than that in
the vehicle group. These results confirm that lipophilic
HMG-CoA reductase inhibitors enhance
myocardial stunning in association with ATP reduction after ischemia and
reperfusion.
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