Hydrogen peroxide decreases effective refractory period in the isolated heart.
Although previous investigations have concluded that reactive oxygen metabolites contribute to reperfusion arrhythmias, the experimental models employed also had a significant amount of tissue injury, which may have contributed to the observed electrophysiologic effects. We studied whether exposure of the intact heart to a reactive oxygen metabolite at doses that are not associated with histologic evidence of cell necrosis would alter myocardial refractoriness, suggesting that subtle and reversible oxidative stress could alter myocardial electrophysiologic properties and perhaps contribute to ventricular arrhythmias. Isolated rabbit hearts were perfused for 30 min with low doses of hydrogen peroxide (H2O2), either 10(-5), 5 x 10(-6), or 10(-6)-M H2O2 versus vehicle alone; followed by a 30-min washout period without H2O2. Infusion of H2O2 for 30 min decreased ventricular epicardial effective refractory period (ERP) in a dose-dependent manner compared to saline controls (delta ERP). The delta ERP versus time curves during the last 10 min of H2O2 infusion were different (p less than 0.01) for each of the three H2O2 doses. Creatine phosphokinase and reversible oxidized glutathione release occurred during 10(-5)-M H2O2 infusion, but not with lower H2O2 doses. Exposure of the intact heart to low concentrations of H2O2, in a range that caused subtle oxidative injury, decreased ventricular ERP in a dose-dependent manner. Thus, H2O2 generation could contribute to ventricular arrhythmias, even in settings of sublethal and potentially reversible oxidative injury.
Lesnefsky
E J
EJ
Division of Cardiology, Case Western Reserve University, Cleveland, OH 44106.
Williams
G R
GR
Rubinstein
J D
JD
Hogue
T S
TS
Horwitz
L D
LD
Reiter
M J
MJ
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology; D004594:Electrophysiology; D005260:Female; D016166:Free Radical Scavengers; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D015425:Myocardial Reperfusion; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide