Acetaminophen and low-flow myocardial ischemia: Efficacy and antioxidant mechanisms

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In the current study, the cardioprotective efficacy of 0.35 mmol/1 acetaminophen administered 10 min after the onset of a 20-min period of global, low-flow myocardial ischemia was investigated. Matched control hearts were administered an equal volume of Krebs-Henseleit physiological buffer solution (vehicle). In separate groups of hearts, the concentration-dependent, negative inotropic properties of hydrogen peroxide and the ability of acetaminophen to attenuate these actions, as well as the effects of acetaminophen on ischemia-reperfusion-mediated protein oxidation, were studied. Acetaminophen-treated hearts regained a significantly greater fraction of baseline, preischemia control function during reperfusion than vehicle-treated hearts. For example, contractility [rate of maximal developed pressure in the left ventricle (±dP/dtmax)] after 10 min of reperfusion was 109 ± 24 and 42 ± 9 mmHg/s (P < 0.05), respectively, in the two groups. The corresponding pressure-rate products were 1,840 ± 434 vs. 588 ± 169 mmHg·beats·min-1 (P < 0.05). Acetaminophen attenuated peroxynitrite-mediated chemiluminescence in the early minutes of reperfusion (e.g., at 6 min, corresponding values for peak light production were ∼8 × 106 counts/min for vehicle vs. <4 × 106 counts/min for acetaminophen, P < 0.05) and the negative inotropic effects of exogenously administered hydrogen peroxide (e.g., at 0.4 mmol/l hydrogen peroxide, pressure-rate products were ∼1.0 × 104 and 3.8 × 103 mmHg· beats·min-1 in acetaminophen- and vehicle-treated hearts, respectively, P < 0.05). Ischemia-mediated protein oxidation was reduced by acetaminophen. The ability of acetaminophen to attenuate the damaging effects of peroxynitrite and hydrogen peroxide and to limit protein oxidation suggest antioxidant mechanisms are responsible for its cardioprotective properties during postischemia-reperfusion.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4 51-4
StatePublished - Jun 29 2002

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


  • Coronary circulation
  • Hydrogen peroxide
  • Peroxynitrite
  • Ventricular function

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