Antioxidant properties of acetaminophen and cardioprotection.
The acute administration of acetaminophen to isolated, perfused guinea pig hearts appears to have cardioprotective effects against the injury/mechanical dysfunction caused by global, low-flow, myocardial ischemia and reperfusion. In the current study we selected ischemia/reperfusion and administration of sodium pentobarbital as perturbations of the electrical stability of the myocardium. We investigated their ability to induce ventricular arrhythmias and changes in the characteristics of monophasic action potentials in the absence and presence of acetaminophen (0.35 mmol/l). The numbers of ventricular premature beats and ventricular salvos encountered in the presence of pentobarbital were significantly (P < 0.05) reduced by acetaminophen. The combined frequency of these arrhythmias was 0.14+/-0.06/min vs 0.03+/-0.01/min (P < 0.05) in the absence and presence of acetaminophen, respectively. The incidence of ventricular salvos increased steadily in vehicle-treated hearts after administration of pentobarbital. No such trend was seen with acetaminophen. After 10 min of global, low-flow myocardial ischemia, MAP50 and MAP90 (monophasic action potentials at 50 and 90% repolarization, respectively) decreased without acetaminophen (e.g. MAP50, 31+/-4 ms) but did not change during the same time interval with acetaminophen (e.g. MAP50, 57+/-6 ms)(P < 0.05). During ischemia and reperfusion, acetaminophen attenuated the release of hydroxyl radicals and peroxynitrite. Collectively these data reveal cardioprotective, antioxidant behavior of acetaminophen. Under selected conditions (e.g. those causing release of free radicals and other oxidants) such behavior might also prevent ventricular arrhythmias.
Merrill
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Department of Cell Biology and Neurosciences, Rutgers University, Piscataway, NJ 08854-8082, USA. merrill@biology.rutgers.edu
Goldberg
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D000082:Acetaminophen / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005260:Female; D018757:GABA Modulators; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects; D017665:Hydroxyl Radical / Q000032:analysis; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy*; D009206:Myocardium / Q000737:chemistry; D010424:Pentobarbital; D030421:Peroxynitrous Acid / Q000032:analysis; D018879:Ventricular Premature Complexes / Q000139:chemically induced / Q000188:drug therapy
D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D002316:Cardiotonic Agents; D018757:GABA Modulators; D030421:Peroxynitrous Acid; D017665:Hydroxyl Radical; D000082:Acetaminophen; D010424:Pentobarbital