Document Detail


Sodium channel enhancer restores baroreflex sensitivity in conscious dogs with heart failure.
MedLine Citation:
PMID:  15563539     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We compared the cardiac inotropic, lusitropic, and chronotropic responses to the Na(+) channel enhancer LY-368052 in conscious dogs before and after development of congestive heart failure (CHF). We also examined the effect of LY-368052 on baroreflex sensitivity and the efferent neural mechanisms of the bradycardic response in heart failure. Dogs were chronically instrumented, and heart failure was induced by right ventricular pacing at 240 beats/min for 3-4 wk. LY-368052 dose-dependently increased left ventricular contractile performance before and after the development of CHF to a similar extent. The inotropic effect of LY-368052 in heart failure was not altered by either ganglionic or beta-adrenergic receptor blockade. LY-368052 improved cardiac relaxation and induced bradycardia in dogs with heart failure but not in normal dogs. The negative chronotropic effect of LY-368052 was eliminated by ganglionic blockade but not beta-adrenergic blockade, suggesting that the bradycardia was mediated by the autonomic nervous system via enhanced parasympathetic tone. Baroreflex sensitivity was assessed as the pulse interval-mean arterial pressure slope in response to temporary pharmacological (nitroglycerin or phenylephrine) and mechanical (brief occlusion of inferior vena cava) alterations of arterial pressure in conscious dogs before and after development of heart failure. Baroreflex sensitivity was significantly depressed in heart failure and restored completely by acute treatment with LY-368052. Thus the Na(+) channel enhancer LY-368052 maintains its beta-receptor-independent inotropic effect in chronic CHF and specifically improves ventricular relaxation and depressed baroreflex function.
Authors:
Weiqun Shen; Robert M Gill; Jian-Ping Zhang; Bonita D Jones; Angela K Corbly; Mitchell I Steinberg
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Publication Detail:
Type:  Journal Article     Date:  2004-11-24
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  288     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-17     Completed Date:  2005-04-20     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1508-14     Citation Subset:  IM    
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. shen_weiqun@lilly.com
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / pharmacology
Animals
Azetidines / pharmacology*
Baroreflex / drug effects*,  physiology
Blood Pressure
Bradycardia / drug therapy,  physiopathology
Cardiotonic Agents / pharmacology*
Consciousness
Dogs
Electrocardiography
Ganglionic Blockers / pharmacology
Heart Failure / drug therapy*,  physiopathology*
Male
Mandelic Acids / pharmacology*
Receptors, Adrenergic, beta / physiology
Sodium Channels / physiology*
Ventricular Function, Left
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Azetidines; 0/Cardiotonic Agents; 0/Ganglionic Blockers; 0/LY368052; 0/Mandelic Acids; 0/Receptors, Adrenergic, beta; 0/Sodium Channels

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


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