The effect of hypochlorous acid and hydrogen peroxide on coronary flow and arrhythmogenesis in myocardial ischemia and reperfusion.
The purpose of this study was to investigate the effect of the oxidants hypochlorous acid (HOCl) and hydrogen peroxide (H2O2) on the vulnerability of the myocardium to reperfusion-induced arrhythmias following global ischemia. After a 15 min equilibration period with or without experimental intervention, isolated perfused rat hearts in the Langendorff mode were made globally ischemic for 5 min by cross-clamping the aortic line. No dysrhythmias were evoked upon reperfusion at the 5 min global ischemia time period. HOCl or H2O2 were added to the perfusate 5 min into the equilibration period with a total exposure of 10 min. Global ischemia was then induced for 5 min followed by 10 min of reperfusion. A dose-response curve for HOCl (50-200 microM) indicated the development of idioventricular rhythms, in a concentration-dependent way. Furthermore, coronary flow of the hearts exposed to 100 and 200 microM HOCl, at 5 min post-reperfusion, was decreased; methionine (10 microM to 1 mM), an accepted scavenger for HOCl, prevented the responses to 200 microM HOCl, in a concentration-dependent manner. All hearts exposed to 200 microM H2O2 developed ventricular dysrhythmias during the reperfusion period. Coronary flow increased after 5 min of exposure to 200 microM H2O2 and remained elevated during reperfusion. It is concluded that toxic oxygen derived products are capable of increasing the susceptibility of the myocardium to reperfusion induced arrhythmias, and that although the electrical responses to exposure to those two oxidants were similar, the effects on the vasculature were not the same.
Okabe
E
E
Department of Pharmacology, Kanagawa Dental College, Japan.
Takahashi
S
S
Norisue
M
M
Manson
N H
NH
Kukreja
R C
RC
Hess
M L
ML
Ito
H
H
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006997:Hypochlorous Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008715:Methionine / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D006997:Hypochlorous Acid; D008715:Methionine; D006861:Hydrogen Peroxide