Key result
Hydrogen peroxide drives rapid electrophysiological dysfunction, an effect accelerated by iron and prevented by desferrioxamine.
Why the study?
Oxygen free radicals have been proposed to trigger reperfusion arrhythmias, but the mechanism of these arrhythmias is unclear.
Does iron catalysis mediate hydrogen peroxide-induced electrophysiological alterations in isolated guinea pig ventricular muscle?
Does iron catalysis mediate hydrogen peroxide-induced electrophysiological alterations in isolated guinea pig ventricular muscle?
Answers are grounded in this paper and cite their sources.
Demonstrates that H2O2-induced electrophysiological abnormalities in ventricular muscle are mediated by intracellular hydroxyl radicals formed via the iron-catalyzed Fenton reaction.
Study objective It has been proposed that oxygen free radicals trigger reperfusion arrhythmias. The mechanism of these arrhythmias is not clear. Thus, the effect of H2O2 on cellular action potentials was examined. Design Trabecular muscles were superfused either with H2O2 alone or with H2O2 in combination either with H2O2 alone or with H2O2 in combination with iron ions or an iron chelating agent or various scavengers of oxygen free radicals. The effect of reduction of the superfusate calcium from 1.8 to 0.2 mmol.litre-1 on H2O2 induced changes was also studied. Experimental material Thin trabecular muscles isolated from the hearts of guinea pigs (200-300 g) of either sex were used. Measurements and main results H2O2 (0.6 mmol.litre-1) caused a reproducible sequence of changes consisting of an initial increase in plateau height and in action potential duration, followed after 12-14 min by rapid action potential shortening accompanied by resting membrane depolarisation, reduction in action potential amplitude and dV/dt max, and by occasional appearance of late afterdepolarisations, leading finally to loss of excitability. This sequence of changes was: (1) accelerated by higher concentrations of H2O2, FeCl3 (0.1 mmol.litre-1), and FeCl2 (0.1 mmol.litre-1); (2) prevented by dimethylthiourea (10 mmol.litre-1) and desferrioxamine (2 mmol.litre-1); (3) not influenced by superoxide dismutase (150 units.ml-1), mannitol (5-50 mmol.litre-1) or PBN (50 mumols.litre-1); and (4) not prevented by a reduction of the superfusate calcium. Conclusions The electrophysiological alterations induced by H2O2 are caused by a hydroxyl radical formed intracellularly in the iron catalysed Fenton reaction.
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Firek et al. (1990) studied Reperfusion arrhythmias (preclinical model). Hydrogen peroxide (H2O2) alone or combined with iron ions, iron chelators, or free radical scavengers vs. H2O2 alone or with various scavengers (superoxide dismutase, mannitol, PBN) or reduced superfusate calcium (0.2 mmol.litre-1) was evaluated on Cellular action potential changes (plateau height, action potential duration, resting membrane potential, amplitude, dV/dt max, late afterdepolarisations, and excitability). H2O2 (0.6 mmol/L) caused action potential shortening, depolarization, and loss of excitability after 12-14 min, which was accelerated by iron and prevented by desferrioxamine.
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