Document Detail


Verapamil ameliorates the clinical and pathological course of murine myocarditis.
MedLine Citation:
PMID:  1331179     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of the calcium channel blocking agent, verapamil, were studied in a murine model of viral myocarditis. Three groups of 8-wk-old DBA/2 mice (n = 25 each) were inoculated with 10 plaque-forming units of encephalomyocarditis virus and randomized to three treatment regimens. Group 1 mice received verapamil intraperitoneally (5 mg/kg per d) for 7 d before infection, followed by verapamil orally (mean dose of 3.5 mg/mouse per d) in drinking water during infection. Group 2 mice received only verapamil orally starting on day 4 after infection, coincident with peak viremia. Group 3 (infected control) received no verapamil in regular drinking water after viral inoculation. Additional control animals were studied in group 4 (n = 21), consisting of uninfected control animals receiving intraperitoneal and oral verapamil at doses identical to group 1, and in group 5 (n = 21), consisting of uninfected and untreated controls. Animals were randomly killed from each group (n = 7) at 7, 14, and 28 d after infection. Routine histology was performed blindly on an apical slice of each heart and semi-quantitatively graded for inflammation, necrosis, calcification, and fibrosis on a scale of 0-4. Digital planimetry was performed to measure the absolute and relative areas of inflammation and necrosis. The pretreated animals in group 1 showed marked reduction in inflammation and necrosis (score of 3.7 +/- 1.4 vs. 8.7 +/- 2.0 in group 3 on day 14, P < 0.05) and were indistinguishable from the posttreated group 2 mice (score of 4.0 +/- 1.5 vs. 8.7 +/- 2.0 in group 3 on day 14, P < 0.05). All the uninfected control animals (groups 4 and 5) showed no myocardial lesions whether treated with verapamil or not. Quantitative planimetry confirmed decreased inflammation and necrosis (2.0 +/- 3.3% in group 1 and 3.5 +/- 3.1% in group 2 vs. 21.9 +/- 22.6% in group 3 on day 14). Untreated infected hearts injected with liquid silicone rubber exhibited extensive areas of focal microvascular constriction and microaneurysm formation; verapamil treatment in either group 1 or 2 completely abolished these abnormalities, resembling uninfected controls in groups 4 or 5. We conclude that verapamil, whether given before infection or after peak viremia in an encephalomyocarditis model of murine myocarditis, significantly reduces the microvascular changes and myocardial necrosis, fibrosis, and calcification leading to cardiomyopathy. This suggests the potentially important role of calcium and microvascular spasm in the pathogenesis of viral myocarditis leading to dilated cardiomyopathy, and may have future therapeutic implications.
Authors:
R Dong; P Liu; L Wee; J Butany; M J Sole
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  90     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1992 Nov 
Date Detail:
Created Date:  1992-12-22     Completed Date:  1992-12-22     Revised Date:  2010-09-07    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2022-30     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Toronto Hospital, University of Toronto, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiomyopathy, Dilated / drug therapy
Encephalomyocarditis virus*
Enterovirus Infections / drug therapy*
Male
Mice
Mice, Inbred DBA
Myocarditis / drug therapy*
Myocardium / pathology
Perfusion
Verapamil / therapeutic use*
Chemical
Reg. No./Substance:
52-53-9/Verapamil
Comments/Corrections

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