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Experimental Biology and Medicine 232:1245-1252 (2007)
doi: 10.3181/0701-RM-19
© 2007 Society for Experimental Biology and Medicine


ORIGINAL RESEARCH ARTICLE

Antiarrhythmic Properties of Acetaminophen in the Dog

Gary F. Merrill*,1, Jared H. Merrill{dagger}, Roseli Golfetti*, Kathryn M. Jaques*, Norell S. Hadzimichalis*, Sunanda S. Baliga* and Tyler H. Rork{ddagger}

* Division of Life Sciences, Department of Cell Biology and Neurosciences, Rutgers University, Piscataway, New Jersey 08854; {dagger} University of Utah Medical Center, Huntsman Cancer Institute, Salt Lake City, Utah 84112; and {ddagger} Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia 22908

To whom requests for reprints should be addressed at 1 Division of Life Sciences, Department of Cell Biology and Neurosciences, Rutgers University, 604 Allison Road, Piscataway, NJ 08854. E-mail: Merrill{at}biology.rutgers.edu

Mongrel dogs bred for research and weighing 25 ± 3 kg were used to test the hypothesis that acetaminophen has antiar-rhythmic properties. Only ventricular arrhythmias defined by the Lambeth Conventions were investigated. Dogs were exposed either to 60 mins of regional myocardial ischemia followed by 180 mins of reperfusion (n = 14) or were administered a high dose of ouabain (n = 14). Both groups of 14 dogs were further divided into vehicle and acetaminophen treatment groups (n = 7 in each). During selected 10-min intervals, we recorded the numbers of ventricular premature beats, ventricular salvos, ventricular bigeminy, ventricular tachycardia (nonsustained and sustained), and we recorded the heart rate, systemic arterial blood pressure, and left ventricular function. Neither heart rate nor the number of ventricular arrhythmias differed significantly under baseline conditions. Conversely, the combined average number of ventricular ectopic beats during ischemia and reperfusion was significantly less in the presence of acetaminophen (28 ± 4 vs. 6 ± 1; P < 0.05). Similarly, percent ectopy during reperfusion in vehicle- and acetaminophen-treated dogs was 1.4 ± 0.4 and 0.4 ± 0.2, respectively (P < 0.05). The number of all ventricular ectopic beats except ventricular salvos was also significantly reduced in the presence of acetaminophen. Similar results were obtained with ouabain. Our results reveal that systemic administration of a therapeutic dose of acetaminophen has previously unreported antiarrhythmic effects in the dog.

Key Words: ouabain • arrhythmogenesis • canine myocardium • ischemia/reperfusion injury







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