Document Detail

Simvastatin alleviates myocardial contractile dysfunction and lethal ischemic injury in rat heart independent of cholesterol-lowering effects.
MedLine Citation:
PMID:  19627175     Owner:  NLM     Status:  MEDLINE    
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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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Physiological research / Academia Scientiarum Bohemoslovaca     Volume:  58     ISSN:  0862-8408     ISO Abbreviation:  Physiol Res     Publication Date:  2009  
Date Detail:
Created Date:  2009-07-24     Completed Date:  2009-09-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9112413     Medline TA:  Physiol Res     Country:  Czech Republic    
Other Details:
Languages:  eng     Pagination:  449-54     Citation Subset:  IM    
1Department of Pharmacology and Toxicology, Facultyof Pharmacy Comenius University, Bratislava, Slovak Republic.
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MeSH Terms
Arrhythmias, Cardiac / etiology,  pathology,  physiopathology,  prevention & control*
Cardiotonic Agents / pharmacology*
Cholesterol / blood
Diabetes Mellitus, Experimental / complications,  drug therapy*,  pathology,  physiopathology
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
Hypercholesterolemia / complications,  drug therapy*,  pathology,  physiopathology
Myocardial Contraction / drug effects*
Myocardial Infarction / etiology,  pathology,  physiopathology,  prevention & control*
Myocardial Ischemia / etiology,  pathology,  physiopathology,  prevention & control*
Myocardium / pathology*
Rats, Wistar
Recovery of Function
Simvastatin / pharmacology*
Ventricular Pressure / drug effects
Reg. No./Substance:
0/Cardiotonic Agents; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 57-88-5/Cholesterol; 79902-63-9/Simvastatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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