Possible underlying mechanism for hydrogen peroxide-induced electromechanical suppression in human atrial myocardium.
Hydrogen peroxide (H(2)O(2)) and its metabolites have been shown to exert complex effects on the cardiac muscle during cardiac ischemia/reperfusion. The aim of the present study, by perfusing H(2)O(2) or/and different scavengers of oxygen free radicals (OFRs) into the human atrium, is to characterize the electropharmacological effects of H(2)O(2) and explore its possible underlying mechanism. Atrial tissues obtained from the heart of 19 patients undergoing corrective cardiac surgery were used. Transmembrane action potentials were recorded using the conventional microelectrode technique, and contraction of atrial fibers was evaluated in normal [K](o) (4 mM) in the absence and presence of tested agents. H(2)O(2) (30 micro M-3 mM) had a biphasic effect on the contractile force (an increase, followed by a decrease), reduced the 0-phase depolarizing slope (dV/dt), and prolonged the action potential duration (APD) in a concentration-dependent manner. However, even at a concentration as high as 3 mM, H(2)O(2) did not influence diastolic membrane potential (DMP). Pretreatment with N-(mercaptopropionyl)-glycine (N-MPG), a specific scavenger of the. OH free radical, significantly blocked the 3 mM H(2)O(2)-induced electromechanical changes, while the pretreatment with L-methionine (L-M), a specific scavenger of HOCl free radical, did not. Our data suggests that the toxic effects of H(2)O(2) are caused mainly through the generation of. OH, which is attributed to the electropharmacological inhibitory effects seen in the human atrium.
Loh
Shih-Hurng
SH
Departments of Pharmacology, National Defense Medical Center. Taipei, Taiwan. shloh@ndmctsgh.edu.tw
Jin
Jong-Shiaw
JS
Tsai
Chien-Sung
CS
Chao
Chao-Ming
CM
Tsai
Yin
Y
Chen
Wei-Hwa
WH
Cheng
Tzu-Hurng
TH
Chuang
Chao-Chin
CC
Lin
Cheng-I
CI
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D005609:Free Radicals / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008715:Methionine / Q000494:pharmacology; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium; D016877:Oxidants / Q000494:pharmacology*; D008625:Tiopronin / Q000494:pharmacology
D000975:Antioxidants; D005609:Free Radicals; D016877:Oxidants; D008715:Methionine; D006861:Hydrogen Peroxide; D008625:Tiopronin