Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A
(HMG-CoA) reductase, are most frequently used drugs in the
prevention of coronary artery disease due to their cholesterollowering activity. However, it is not exactly known whether these
effects of statins or those independent of cholesterol decrease
account for the protection against myocardial ischemiareperfusion (I/R) injury. In this study, we investigated the effect
of 5-day treatment with simvastatin (10 mg/kg) in Langendorffperfused hearts of healthy control (C) and diabetichypercholesterolemic (D-H; streptozotocin + high fat-cholesterol
diet, 5 days) rats subjected to 30-min global ischemia followed
by 40-min reperfusion for the examination of postischemic
contractile dysfunction and reperfusion-induced ventricular
arrhythmias or to 30-min (left anterior descending) coronary
artery occlusion and 2-h reperfusion for the infarct size
determination (IS; tetrazolium staining). Postischemic recovery of
left ventricular developed pressure (LVDP) in animals with D-H
was improved by simvastatin therapy (62.7±18.2 % of
preischemic values vs. 30.3±5.7 % in the untreated D-H;
P<0.05), similar to the values in the simvastatin-treated C group,
which were 2.5-fold higher than those in the untreated C group.
No ventricular fibrillation occurred in the simvastatin-treated C
and D-H animals during reperfusion. Likewise, simvastatin
shortened the duration of ventricular tachycardia (10.2±8.1 s and
57.8±29.3 s in C and D-H vs. 143.6±28.6 s and 159.3±44.3 s in
untreated C and D-H, respectively, both P<0.05). The decreased
arrhythmogenesis in the simvastatin-treated groups correlated
with the limitation of IS (in % of risk area) by 66 % and 62 % in
C and D-H groups, respectively. However, simvastatin treatment
decreased plasma cholesterol levels neither in the D-H animals
nor in C. The results indicate that other effects of statins
(independent of cholesterol lowering) are involved in the
improvement of contractile recovery and attenuation of lethal I/R
injury in both, healthy and diseased individuals.