Document Detail


Coronary and myocardial effects of acetaminophen: protection during ischemia-reperfusion.
MedLine Citation:
PMID:  11356619     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acetaminophen is a phenol with antioxidant properties, but little is known about its actions on the mammalian myocardium and coronary circulation. We studied isolated, perfused guinea pig hearts, and tested the hypothesis that acetaminophen-treated hearts would be protected during ischemia-reperfusion. Acetaminophen concentrations in the range of 0.3-0.6 mmol/l caused modest but significant (P < 0.05) coronary vasoconstriction and positive inotropy. The effects were more brisk during constant pressure perfusion than during constant flow. During 20 min of low-flow, global myocardial ischemia and 40 min of reperfusion, hearts treated with acetaminophen retained or recovered a greater percentage of left ventricular function than hearts treated with vehicle. Myofibrillar ultrastructure appeared to be preserved in the reperfused myocardium with acetaminophen. By using chemiluminescence and spin-trap methodologies, we investigated acetaminophen-mediated antioxidant mechanisms to help explain the cardioprotection. The burst of hydroxyl radicals seen between 0 and 10 min of reperfusion was significantly attenuated (P < 0.05) by acetaminophen but not by vehicle. The 3-morpholinosydnominine (SIN-1) generation of peroxynitrite and its oxidative interaction with luminol to produce blue light during ischemia-reperfusion was also blocked by acetaminophen. Our results show that acetaminophen provides significant functional and structural protection to the ischemic-reperfused myocardium, and the mechanism of cardioprotection seems to involve attenuation of the production of both hydroxyl radicals and peroxynitrite.
Authors:
G Merrill; P McConnell; K Vandyke; S Powell
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  280     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-05-17     Completed Date:  2001-06-14     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:  H2631-8     Citation Subset:  IM    
Affiliation:
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854-8082, USA. merrill@biology.rutgers.edu
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MeSH Terms
Descriptor/Qualifier:
Acetaminophen / pharmacology*
Animals
Chemiluminescent Measurements
Coronary Circulation / drug effects
Coronary Vessels / drug effects
Cytoprotection / drug effects*
Dose-Response Relationship, Drug
Female
Gentisates*
Guinea Pigs
Heart / drug effects
Heart Rate / drug effects
Hydroxybenzoic Acids / metabolism
Hydroxyl Radical / metabolism
Male
Myocardial Ischemia / metabolism*
Myocardial Reperfusion
Myocardial Reperfusion Injury / prevention & control*
Myocardium / metabolism*,  ultrastructure
Myofibrils / drug effects,  ultrastructure
Nitrates / metabolism
Perfusion / methods
Vasoconstriction / drug effects
Ventricular Function, Left / drug effects
Chemical
Reg. No./Substance:
0/Gentisates; 0/Hydroxybenzoic Acids; 0/Nitrates; 103-90-2/Acetaminophen; 26404-66-0/peroxynitric acid; 3352-57-6/Hydroxyl Radical; 490-79-9/2,5-dihydroxybenzoic acid

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


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