Document Detail


Cardiovascular effects of acute hypercholesterolemia in rabbits. Reversal with lovastatin treatment.
MedLine Citation:
PMID:  2913050     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypercholesterolemia was induced in New Zealand white rabbits by feeding them a 0.5% cholesterol-enriched rabbit chow for 2 wk. Half of the cholesterol-fed rabbits were given lovastatin, a potent inhibitor of hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate limiting enzyme in cholesterol biosynthesis, and the other half were given its vehicle (i.e., DMSO). At the end of 2 wk, the rabbits underwent experimental myocardial ischemia or a sham ischemia procedure. Ischemic animals fed the cholesterol-enriched diet for 2 wk experienced much greater cardiac damage than ischemic rabbits fed the control diet, despite the absence of any atherosclerosis. Lovastatin was shown to protect the ischemic rabbit myocardium by three different indices of ischemic damage: (a) maintenance of creatine kinase (CK) activity in the ischemic myocardium; (b) reduced loss of free amino-nitrogen containing compounds from the ischemic myocardium; and (c) blunting the rise of plasma CK activity. These effects were not due to differences in myocardial oxygen demand between the groups. Arteries isolated from animals fed the cholesterol-enriched diet developed defects in endothelium-dependent relaxation in both large vessels as well as coronary resistance vessels. Acute hypercholesterolemia increases the severity of myocardial ischemia while at the same time impairing endothelium-dependent relaxation. These deleterious changes can be significantly attenuated by treatment with lovastatin.
Authors:
J A Osborne; P H Lento; M R Siegfried; G L Stahl; B Fusman; A M Lefer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  83     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1989 Feb 
Date Detail:
Created Date:  1989-03-09     Completed Date:  1989-03-09     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  465-73     Citation Subset:  AIM; IM    
Affiliation:
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiovascular System / physiopathology*
Cholesterol, Dietary / administration & dosage
Coronary Disease / complications,  physiopathology
Creatine Kinase / metabolism
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypercholesterolemia / drug therapy,  physiopathology*
Isoenzymes
Lovastatin / therapeutic use*
Male
Myocardium / enzymology
Rabbits
Grant Support
ID/Acronym/Agency:
HL-07599/HL/NHLBI NIH HHS; HL-25575/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cholesterol, Dietary; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Isoenzymes; 75330-75-5/Lovastatin; EC 2.7.3.2/Creatine Kinase
Comments/Corrections

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