title: Acetaminophen is cardioprotective against H2O2-induced injury in vivo.
abstract: Here we report our ongoing investigation of the cardiovascular effects of acetaminophen, with emphasis on oxidation-induced canine myocardial dysfunction. The objective of the current study was to investigate whether acetaminophen could attenuate exogenous H(2)O(2)-mediated myocardial dysfunction in vivo. Respiratory, metabolic, and hemodynamic indices such as left ventricular function (LVDP and +/-dP/dt(max)), and percent ectopy were measured in anesthetized, open-chest dogs during intravenous administration of 0.88 mM, 2.2 mM, 6.6 mM H(2)O(2). Following 6.6 mM H(2)O(2), tissue from the left ventricle was harvested for electron microscopy. Left ventricular function did not vary significantly between vehicle and acetaminophen groups under baseline conditions. Acetaminophen-treated dogs regained a significantly greater fraction of baseline function after high concentrations of H(2)O(2) than vehicle-treated dogs. Moreover, the incidence of H(2)O(2)-induced ventricular arrhythmias was significantly reduced in the acetaminophen-treated group. Percent ectopy following 6.6 mM concentrations of H(2)O(2) was 1 +/- 0.3 vs. 0.3 +/- 0.1 (P < 0.05) for vehicle- and acetaminophen-treated dogs, respectively. Additionally, electron micrograph images of left ventricular tissue confirmed preservation of tissue ultrastructure in acetaminophen-treated hearts when compared to vehicle. We conclude that, in the canine myocardium, acetaminophen is both functionally cardioprotective and antiarrhythmic against H(2)O(2)-induced oxidative injury.
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Jaques-Robinson
authors.forename: Roseli
authors.initials: R
authors.lastname: Golfetti
authors.forename: Sunanda S
authors.initials: SS
authors.lastname: Baliga
authors.forename: Norell M
authors.initials: NM
authors.lastname: Hadzimichalis
authors.forename: Gary F
authors.initials: GF
authors.lastname: Merrill
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D006861:Hydrogen Peroxide / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D006861:Hydrogen Peroxide