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January 1, 2003Journal of Pharmacological Sciences14 citationsOpen Access

Possible Underlying Mechanism for Hydrogen Peroxide-Induced Electromechanical Suppression in Human Atrial Myocardium

SLShih‐Hurng LohJJJong‐Shiaw JinCTChien‐Sung Tsai

Key Result

Hydrogen peroxide induced concentration-dependent electromechanical suppression in human atrial myocardium, which was significantly blocked by the hydroxyl radical scavenger N-MPG.

Structured PICO

Does hydrogen peroxide and oxygen free radical scavengers alter electromechanical parameters in human atrial myocardium?

P
Population
Atrial tissues from 19 patients (52.6% female) undergoing open-heart surgery were used to evaluate the electromechanical effects of hydrogen peroxide.
I
Intervention
Perfusion with hydrogen peroxide (H2O2) (30 microM - 3 mM) and/or oxygen free radical scavengers (N-MPG 10 mM, L-methionine 1 mM)
C
Comparator
Control Tyrode solution (baseline/drug-free superfusate)
O
Outcome
Electromechanical parameters including transmembrane action potentials, contractile force, 0-phase depolarizing slope (dV/dt), and action potential duration (APD)surrogate

H2O2 induces electromechanical suppression in human atrial myocardium primarily through the generation of hydroxyl radicals, which can be prevented by the specific scavenger N-MPG.

Main Result

p-value: p=<0.05

Limitations

  • In vitro experimental design
  • Small sample size of 19 patients
  • Underlying mechanism of increased diastolic resting tension requires further study

Abstract

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.

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Cite This Study

Loh et al. (2003) studied Patients undergoing corrective cardiac surgery (n=19). Hydrogen peroxide (H2O2) vs. Drug-free Tyrode solution was evaluated on Electromechanical suppression (action potential characteristics and contractile force) (p=<0.05). Hydrogen peroxide induced concentration-dependent electromechanical suppression in human atrial myocardium, which was significantly blocked by the hydroxyl radical scavenger N-MPG.

synapsesocial.com/papers/6a904204fdb099d0d8dd7d98https://doi.org/10.1254/jphs.91.53
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