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Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854
In the
current study, the cardioprotective efficacy of 0.35 mmol/l
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 · min1
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.
coronary circulation; ventricular function; peroxynitrite; hydrogen peroxide
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