Document Detail

Effects of simvastatin on cardiohemodynamic responses to ischemia-reperfusion in isolated rat hearts.
MedLine Citation:
PMID:  16550313     Owner:  NLM     Status:  MEDLINE    
Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has long been thought to exert its benefits by reducing cholesterol synthesis, and has been shown to significantly reduce cardiovascular events and mortality in patients with or without coronary artery disease. However, it is still unknown whether acute administration of simvastatin beneficially affects the cardiac function prior or during ischemia-reperfusion. The aim of this study is to evaluate the cardioprotective effect of acute simvastatin treatment on isolated rat hearts or isolated ischemia-reperfusion hearts. Hearts were isolated from male Sprague-Dawley rats and attached to a Langendorff apparatus. The isolated hearts with or without ischemia (15 min) and reperfusion (60 min) were perfused with different concentrations of simvastatin. The parameters of cardiac function (such as left ventricular developed pressure [LVDP], +dp/dt max, and -dp/dt max), heart rate, and coronary flow were recorded. Simvastatin (3-30 micromol/l) significantly increased LVDP, +dp/dt max, and -dp/dt max in isolated rat hearts perfused for 60 min. Heart rate was depressed by 30 micromol/l simvastatin and the coronary flow was increased by 10 and 30 micromol/l simvastatin. At a concentration of 100 micromol/l simvastatin, worsening of heart function and subsequent cardiac arrest occurred. Administration of simvastatin (3-30 micromol/l) significantly preserved cardiac function detected by LVDP, +dp/dt max, and -dp/dt max in the isolated ischemia/reperfused (15/60 min) rat hearts. Simvastatin also significantly decreased heart rate at 30 micromol/l, and increased coronary flow at 10 and 30 micromol/l in these rat hearts. However, the protective effect of simvastatin reverted to increased damage at 100 micromol/l. Only 3 micromol/l simvastatin pretreatment before 15/60 min ischemia-reperfusion altered LVDP, +dp/dt max, and -dp/dt max. Both heart rate and coronary flow were unaltered after simvastatin pretreatment. Since simvastatin at a concentration lower than 100 micromol/l exerted beneficial effects on cardiac function in isolated perfused rat hearts, it could be applied just after myocardial ischemia and reperfusion.
Xia Zheng; Shen-Jiang Hu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Heart and vessels     Volume:  21     ISSN:  0910-8327     ISO Abbreviation:  Heart Vessels     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-21     Completed Date:  2007-05-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8511258     Medline TA:  Heart Vessels     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  116-23     Citation Subset:  IM    
Cardiovascular Department, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
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MeSH Terms
Analysis of Variance
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Myocardial Ischemia / drug therapy*,  pathology,  physiopathology
Myocardial Reperfusion Injury / drug therapy*,  pathology,  physiopathology
Random Allocation
Rats, Sprague-Dawley
Simvastatin / pharmacology*
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 79902-63-9/Simvastatin

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