Hydrogen peroxide induced changes in membrane potentials in guinea pig ventricular muscle: permissive role of iron.
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.


METHODS
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.


METHODS
Thin trabecular muscles isolated from the hearts of guinea pigs (200-300 g) of either sex were used.


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.
Firek
L
L
Department of Clinical Physiology, Medical Centre of Postgraduate Education, Warsaw, Poland.
Beresewicz
A
A
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003497:Cyclic N-Oxides; D005260:Female; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009589:Nitrogen Oxides / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D016276:Ventricular Function
D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase