Document Detail


Niacin protects the isolated heart from ischemia-reperfusion injury.
MedLine Citation:
PMID:  10924076     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nicotinic acid (niacin) has been shown to decrease myocyte injury. Because interventions that lower the cytosolic NADH/NAD(+) ratio improve glycolysis and limit infarct size, we hypothesized that 1) niacin, as a precursor of NAD(+), would lower the NADH/NAD(+) ratio, increase glycolysis, and limit ischemic injury and 2) these cardioprotective benefits of niacin would be limited in conditions that block lactate removal. Isolated rat hearts were perfused without (Ctl) or with 1 microM niacin (Nia) and subjected to 30 min of low-flow ischemia (10% of baseline flow, LF) and reperfusion. To examine the effects of limiting lactate efflux, experiments were performed with 1) Ctl and Nia groups subjected to zero-flow ischemia and 2) the Nia group treated with the lactate-H(+) cotransport inhibitor alpha-cyano-4-hydroxycinnamate under LF conditions. Measured variables included ATP, pH, cardiac function, tissue lactate-to-pyruvate ratio (reflecting NADH/NAD(+)), lactate efflux rate, and creatine kinase release. The lactate-to-pyruvate ratio was reduced by more than twofold in Nia-LF hearts during baseline and ischemic conditions (P < 0.001 and P < 0.01, respectively), with concurrent lower creatine kinase release than Ctl hearts (P < 0.05). Nia-LF hearts had significantly greater lactate release during ischemia (P < 0.05 vs. Ctl hearts) as well as higher functional recovery and a relative preservation of high-energy phosphates. Inhibiting lactate efflux with alpha-cyano-4-hydroxycinnamate and blocking lactate washout with zero flow negated some of the beneficial effects of niacin. During LF, niacin lowered the cytosolic redox state and increased lactate efflux, consistent with redox regulation of glycolysis. Niacin significantly improved functional and metabolic parameters under these conditions, providing additional rationale for use of niacin as a therapeutic agent in patients with ischemic heart disease.
Authors:
N A Trueblood; R Ramasamy; L F Wang; S Schaefer
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  279     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-09-12     Completed Date:  2000-09-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H764-71     Citation Subset:  IM    
Affiliation:
Division of Cardiovascular Medicine, Department of Medicine, University of California, Davis, California 95616, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure
Creatine Kinase / metabolism
Fatty Acids, Nonesterified / metabolism
Heart / drug effects*,  physiology,  physiopathology
Heart Rate
Lactates / analysis
Male
Myocardial Ischemia / physiopathology
Myocardial Reperfusion Injury / physiopathology,  prevention & control*
NAD / metabolism
Niacin / pharmacology*
Pyruvates / metabolism
Rats
Rats, Sprague-Dawley
Ventricular Function, Left
Chemical
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Lactates; 0/Pyruvates; 53-84-9/NAD; 59-67-6/Niacin; EC 2.7.3.2/Creatine Kinase

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


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