Document Detail

Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering.
MedLine Citation:
PMID:  12142124     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES; This study was designed to assess the lipid-independent effects of simvastatin on myocardial perfusion (MP) and coronary microvascular permeability index (PI) at baseline and during episodes of increased cardiac demand in experimental hypercholesterolemia. BACKGROUND: Simvastatin preserves coronary endothelial function in experimental hypercholesterolemia independent of its lipid-lowering effect. However, the functional significance of this observation is unknown. METHODS: Pigs were randomized to three groups: normal diet (N), high-cholesterol diet (HC) and HC diet plus simvastatin (HC+S) for 12 weeks. Subsequently, cardiac electron beam computed tomography was performed before and during intravenous infusion of adenosine and dobutamine, and MP and PI were calculated. RESULTS: Total and low density lipoprotein cholesterol levels were similarly and significantly increased in HC and HC+S animals compared with N. Basal MP was similar in all groups. Myocardial perfusion significantly increased in response to either adenosine or dobutamine in N and HC+S animals. Dobutamine also significantly increased MP in HC animals. However, the changes of MP in response to either drug were significantly lower in the HC group compared with the other two groups (p < 0.01 for adenosine and p < 0.05 for dobutamine vs. N and HC+S). Basal PI was similar in all groups and was not altered by either drug in N and HC+S animals. In contrast, PI significantly increased in HC pigs during infusion of either adenosine (p < 0.001) or dobutamine (p < 0.05). CONCLUSIONS: These findings demonstrate that chronic administration of simvastatin preserves myocardial perfusion response and coronary microvascular integrity during cardiac stress in experimental hypercholesterolemia independent of lipid lowering.
Piero O Bonetti; Stephanie H Wilson; Martin Rodriguez-Porcel; David R Holmes; Lilach O Lerman; Amir Lerman
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Publication Detail:
Type:  Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  40     ISSN:  0735-1097     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-07-26     Completed Date:  2002-08-30     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  546-54     Citation Subset:  AIM; IM    
Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
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MeSH Terms
Anticholesteremic Agents / pharmacokinetics*,  therapeutic use*
Body Weight / physiology
Capillary Permeability / drug effects*
Cholesterol, HDL / blood
Cholesterol, LDL / blood
Coronary Vessels / drug effects*,  physiology*,  ultrasonography
Disease Models, Animal
Hemodynamics / physiology
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*,  therapeutic use*
Hypercholesterolemia / drug therapy*,  ultrasonography
Models, Cardiovascular
Myocardial Ischemia / drug therapy*,  prevention & control*
Random Allocation
Simvastatin / pharmacokinetics*,  therapeutic use*
Stroke Volume / physiology
Tomography, X-Ray Computed
Treatment Outcome
Grant Support
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 79902-63-9/Simvastatin

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