Document Detail

Acetaminophen in the hypoxic and reoxygenated guinea pig myocardium.
MedLine Citation:
PMID:  15564442     Owner:  NLM     Status:  MEDLINE    
We investigated the effects of 0.35-mM acetaminophen and its vehicle on isolated, perfused guinea pig hearts made hypoxic and subsequently reoxygenated. Hearts were allowed 30 min postinstrumentation to reach baseline, steady-state values, and then were exposed to 6 min of hypoxia (5% O(2), 5% CO(2), balance N(2)) followed by 36 min of reoxygenation (95% O(2), 5% CO(2)). We recorded hemodynamic, metabolic, and mechanical data in addition to assessing ultrastructure and the capacity of coronary venous effluent to reduce reactive oxygen species. We found that acetaminophen-treated hearts retained a greater fraction of mechanical function during hypoxia and reoxygenation. For example, the average percentage change from baseline of left ventricular developed pressure in acetaminophen- and vehicle-treated hearts at 6 min reoxygenation was 9 +/- 2% and -8 +/- 5% (P < 0.05), respectively. In addition, electron micrographs revealed greater preservation of myofibrillar ultrastructure in acetaminophen-treated hearts. Biochemical analyses revealed the potential of coronary effluent from acetaminophen-treated hearts to significantly neutralize peroxynitrite-dependent chemiluminescence in all recorded time periods. During early reoxygenation, the percentage inhibition of peroxynitrite-mediated chemiluminescence was 56 +/- 10% in vehicle-treated hearts and 99 +/- 1% in acetaminophen-treated hearts (P < 0.05). We conclude that acetaminophen has previously unreported cardioprotective properties in the nonischemic, hypoxic, and reoxygenated myocardium mediated through the reduction of reactive oxygen species.
Tyler H Rork; Knox Van Dyke; Norell M Spiler; Gary F Merrill
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental biology and medicine (Maywood, N.J.)     Volume:  229     ISSN:  1535-3702     ISO Abbreviation:  Exp. Biol. Med. (Maywood)     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-11-26     Completed Date:  2005-01-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100973463     Medline TA:  Exp Biol Med (Maywood)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1154-61     Citation Subset:  IM    
Division of Life Sciences, Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Rd., Piscataway, NJ 08854, USA.
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MeSH Terms
Acetaminophen / pharmacology*
Anoxia / drug therapy*,  pathology
Cardiotonic Agents / pharmacology*
Guinea Pigs
Heart / drug effects*
Microscopy, Electron, Transmission
Myocardial Contraction / drug effects
Myocardium / pathology*,  ultrastructure
Organ Culture Techniques
Peroxynitrous Acid / metabolism
Reg. No./Substance:
0/Cardiotonic Agents; 103-90-2/Acetaminophen; 14691-52-2/Peroxynitrous Acid

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