Acetaminophen in the hypoxic and reoxygenated guinea pig myocardium.
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.
Rork
Tyler H
TH
Division of Life Sciences, Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Rd., Piscataway, NJ 08854, USA.
Van Dyke
Knox
K
Spiler
Norell M
NM
Merrill
Gary F
GF
D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D000860:Hypoxia / Q000188:drug therapy* / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D030421:Peroxynitrous Acid / Q000378:metabolism
D002316:Cardiotonic Agents; D030421:Peroxynitrous Acid; D000082:Acetaminophen