Firek L, Beresewicz A
Department of Clinical Physiology, Medical Centre of Postgraduate Education, Warsaw, Poland.
Cardiovasc Res. 1990 Jun;24(6):493-9. doi: 10.1093/cvr/24.6.493.
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.
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.
Thin trabecular muscles isolated from the hearts of guinea pigs (200-300 g) of either sex were used.
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.
The electrophysiological alterations induced by H2O2 are caused by a hydroxyl radical formed intracellularly in the iron catalysed Fenton reaction.
有人提出氧自由基会引发再灌注心律失常。这些心律失常的机制尚不清楚。因此，研究了过氧化氢对细胞动作电位的影响。
用单独的过氧化氢或与铁离子、铁螯合剂或各种氧自由基清除剂联合使用的过氧化氢对小梁肌进行灌流。还研究了将灌流液钙浓度从1.8 mmol·升-1降至0.2 mmol·升-1对过氧化氢诱导变化的影响。
使用从雌雄豚鼠（200 - 300克）心脏分离出的细小梁肌。
过氧化氢（0.6 mmol·升-1）引起一系列可重复的变化，包括平台期高度和动作电位持续时间最初增加，12 - 14分钟后动作电位迅速缩短，伴有静息膜去极化、动作电位幅度和最大dV/dt降低，偶尔出现晚期后去极化，最终导致兴奋性丧失。这一系列变化：（1）被更高浓度的过氧化氢、氯化铁（0.1 mmol·升-1）和氯化亚铁（0.1 mmol·升-1）加速；（2）被二甲基硫脲（10 mmol·升-1）和去铁胺（2 mmol·升-1）阻止；（3）不受超氧化物歧化酶（150单位·毫升-1）、甘露醇（5 - 50 mmol·升-1）或PBN（50 μmol·升-1）影响；（4）不被灌流液钙浓度降低所阻止。
过氧化氢诱导的电生理改变是由铁催化的芬顿反应在细胞内形成的羟基自由基引起的。
