Document Detail

Effect of trimetazidine and verapamil on the cardiomyopathic hamster myosin phenotype.
MedLine Citation:
PMID:  9517378     Owner:  NLM     Status:  MEDLINE    
1. In this study we investigated whether long-term trimetazidine (anti-ischaemic drug) therapy alters the ventricular myosin heavy chain (MHC) isoform composition in a model of cardiomyopathy. 2. MHC isoforms were analysed in the native state by electrophoresis in a pyrophosphate buffer. Myosin isoform patterns were studied in cardiac muscle from cardiomyopathic hamsters (CMH) of the BIO 14:6 strain during the time course of the disease and compared with those of healthy golden hamsters (F1B). The correlation between myosin profile and Ca2+-activated ATPase activity was determined from 220 days. 3. At the stage of insufficiency (350 days), CMH presented the most abnormal phenotype with 53% V1-24% V3 compared to 79% V1-7% V3 (P<0.001), in F1B. Trimetazidine was administered to cardiomyopathic hamsters from the early stage of active disease (30 days) to the congestive stages (220-350 days). Within 65 days, trimetazidine treatment, in CMH and F1B, reduced V1 to a low level (53% and 62%, respectively), which remained constant throughout the treatment. This level was similar to that in 220 and 350 days-old untreated-CMH. In sharp contrast, a standard calcium blocker, verapamil, administered to CMH in the same conditions resulted in a higher V1 (about 70%) and higher global myosin ATPase activity from 220 days. 4. Previous results in terms of hypertrophy and survival, compared to these results, suggest that verapamil and trimetazidine treatments reveal a dissociation between ventricular hypertrophy and isomyosin distribution. In addition, the shift in favour of V3 may not necessarily be an aggravating factor of the disease but an adaptative compensatory event.
N D'hahan; K Taouil; C Janmot; J E Morel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  123     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1998 Feb 
Date Detail:
Created Date:  1998-04-16     Completed Date:  1998-04-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  611-6     Citation Subset:  IM    
Laboratoire de Biologie, Ecole Centrale Paris, Châtenay-Malabry, France.
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MeSH Terms
Calcium Channel Blockers / therapeutic use*
Calcium-Transporting ATPases / metabolism
Cardiomyopathies / drug therapy*,  enzymology,  genetics
Electrophoresis, Polyacrylamide Gel
Myosins / genetics*,  isolation & purification
Trimetazidine / therapeutic use*
Vasodilator Agents / therapeutic use*
Verapamil / therapeutic use*
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Vasodilator Agents; 5011-34-7/Trimetazidine; 52-53-9/Verapamil; EC ATPases; EC

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