Simvastatin alleviates myocardial contractile dysfunction and lethal ischemic injury in rat heart independent of cholesterol-lowering effects
Language English Country Czech Republic Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19627175
DOI
10.33549/physiolres.931751
PII: 1751
Knihovny.cz E-resources
- MeSH
- Cholesterol blood MeSH
- Diabetes Mellitus, Experimental complications drug therapy pathology physiopathology MeSH
- Hypercholesterolemia complications drug therapy pathology physiopathology MeSH
- Myocardial Infarction etiology pathology physiopathology prevention & control MeSH
- Myocardial Ischemia etiology pathology physiopathology prevention & control MeSH
- Cardiotonic Agents pharmacology MeSH
- Ventricular Pressure drug effects MeSH
- Myocardial Contraction drug effects MeSH
- Rats MeSH
- Myocardium pathology MeSH
- Recovery of Function MeSH
- Perfusion MeSH
- Rats, Wistar MeSH
- Simvastatin pharmacology MeSH
- Arrhythmias, Cardiac etiology pathology physiopathology prevention & control MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cholesterol MeSH
- Cardiotonic Agents MeSH
- Simvastatin MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH
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 cholesterol-lowering activity. However, it is not exactly known whether these effects of statins or those independent of cholesterol decrease account for the protection against myocardial ischemia-reperfusion (I/R) injury. In this study, we investigated the effect of 5-day treatment with simvastatin (10 mg/kg) in Langendorff-perfused hearts of healthy control (C) and diabetic-hypercholesterolemic (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.
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