Document Detail


Effects of first and second generation calcium channel blockers on diastolic function of the failing hamster heart: relationship with coronary flow changes.
MedLine Citation:
PMID:  12827040     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Calcium channel blockers (CCBs) have variable efficacy in the treatment of heart failure. We hypothesized that modulation of left ventricular diastolic pressure (LVDP) may play a role in the variable efficacy of CCBs in this condition. Isolated perfused hearts from 200- to 250-day-old UM-X7.1 cardiomyopathic hamsters (failing hearts) and age-matched Syrian hamsters (normal hearts) were studied. After recording of heart rate, coronary flow (CF), LVDP and left ventricular systolic pressure (LVSP), hearts were exposed either to verapamil or diltiazem (1 nM-10 microM), mibefradil (1 nM-1 microM) or clentiazem (1 nM-10 microM). Mechanical increase in CF (+2 to +10 ml/min) was carried out using a roller pump. Mechanically-augmented flow led to an increase in coronary perfusion pressure (+40 to +90 mm Hg), LVSP (+5 to +40 mm Hg) and LVDP (+5 to +25 mm Hg). CCBs-induced increment of coronary flow led to a difference in their cardiac response. In normal hearts, the negative inotropic response was more important with diltiazem and verapamil. Failing hearts did not demonstrate increased inotropic sensitivity to first-generation CCBs. On the contrary, at clinically relevant concentrations, verapamil resulted in the most pronounced impairment of LVDP followed by diltiazem while mibefradil and clentiazem, at clinically relevant concentrations, preserved LVDP. Such findings provide an additional explanation for the variable efficacy of CCBs in heart failure.
Authors:
Pierre Beaucage; Julie Massicotte; Jean-François Boileau; Louis Dumont
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  42     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-06-26     Completed Date:  2003-11-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  142-50     Citation Subset:  IM    
Affiliation:
Départements de pharmacologie, Faculté de médecine, Université de Montréal, Quebec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects,  physiology
Calcium Channel Blockers / pharmacology*
Cardiac Output, Low / physiopathology*
Coronary Circulation / drug effects*,  physiology
Cricetinae
Heart* / drug effects,  physiopathology
Ventricular Function, Left / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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