Effect of hydrogen peroxide on intracellular pH in the human atrial myocardium.
The cardiac injury observed during myocardial ischemia and reperfusion has been shown to be a consequence of a complex mechanism in which the accumulation of hydrogen peroxide (H2O2) and other oxygen free radicals (OFRs), and intracellular pH (pHi) are believed to play a major role. However, the effect of H2O2 on pHi has not been well characterized in the human atrial myocardium. In the present study, we superfused hydrogen peroxide into the human atrial tissue in order to assess the effects of oxygen free radicals on the pHi, and, furthermore, to test the ability of certain potential cardioprotective agents, including scavengers of the *OH free radical (N-(mercaptopropionyl)-glycine; N-MPG) and the HOCl free radical (L-methionine), to protect against oxidative-induced pHi challenge. The human atrial tissues were obtained from patients undergoing corrective open-heart surgery. The ratiometric recordings of pHi were measured using the pH-sensitive, dual-excitation and dual-emission fluorescent dye BCECF (2', 7'-bis(carboxyethyl)-5, 6-carboxyfluorescein acetoxymethyl ester). By continuously monitoring pHi changes in human atrial myocardium, we have found, for the first time, that (a) H2O2 (30 microM-3 mM) induced a significant dose-dependent intracellular acidosis, (b) N-MPG caused a significant block on the intracellular acidosis induced by 3 mM H2O2, whereas L-methionine did not, and (c) Hoe 694, a specific Na+/H+ exchanger (NHE) inhibitor, caused a similar extents like that induced by 3 mM H2O2. Our data suggest that the effects of H2O2 are caused mainly through the generation of *OH, which is attributed to the intracellular acidosis seen in the human atrial trabecular muscle. The possible underlying mechanism for H2O2-induced acidosis is likely due to its inhibition on the activity of NHE and other acid extruders, as the pHi changes after H2O2 exposure could be detected even though the activity of NHE was completely blocked by 30 mM Hoe 694.
Chao
Chao-Ming
CM
Department of Dermatology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Jin
Jong-Shiaw
JS
Tsai
Chien-Sung
CS
Tsai
Yin
Y
Chen
Wei-Hwa
WH
Chung
Chao-Chin
CC
Loh
Shih-Hurng
SH
D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism; D000368:Aged; D005260:Female; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
D016877:Oxidants; D017382:Reactive Oxygen Species; D017923:Sodium-Hydrogen Exchangers; D006861:Hydrogen Peroxide