Electrophysiological derangements induced by lipid peroxidation in cardiac tissue.
Electrophysiological derangements induced by lipid peroxidation in cardiac tissue.
复制标题
心脏组织中脂质过氧化引起的电生理紊乱。
作者：
H. Nakaya;N. Tohse;M. Kanno
最近有人推测氧自由基可能参与再灌注诱导的心律失常。本研究旨在评估离体心脏组织中膜脂过氧化引起的细胞电生理变化。在逆行灌注豚鼠心脏，灌注有机氢过氧化物，枯烯过氧化氢（CH），和叔丁基过氧化氢（TBH）引起传导障碍和心律失常，伴随着丙二醛（MDA）含量的增加的心肌。氢过氧化物降低了犬浦肯野纤维和豚鼠乳头肌的最大舒张电位、动作电位振幅和0相最大上升速度。它们还诱导异常自律性，如去极化诱导的自律性，延迟后去极化和触发活动。机械异常，包括增加静息张力和后收缩，推测是由于细胞内Ca2+超载，产生的氢过氧化物。抗氧化剂二丁基羟基甲苯预处理可显著抑制过氧化氢诱导的心肌电生理紊乱和MDA的积累。这些结果表明，膜的脂质过氧化导致各种电生理和机械异常，并可能在再灌注诱导的心律失常的发生中发挥作用。
Recently it has been postulated that oxygen-derived free radicals may be involved in reperfusion-induced arrhythmias. This study was undertaken to evaluate cellular electrophysiological alterations produced by peroxidation of membrane lipids in isolated cardiac tissues. In retrogradely perfused guinea pig hearts, perfusion of organic hydroperoxides, cumene hydroperoxide (CH), and tert-butyl hydroperoxide (TBH) caused conduction disturbances and arrhythmias, concomitantly with an increase in malondialdehyde (MDA) content of the myocardium. The hydroperoxides decreased the maximum diastolic potential, action potential amplitude, and maximum upstroke velocity of phase 0 in both canine Purkinje fibers and guinea pig papillary muscles. They also induced abnormal automaticity, such as depolarization-induced automaticity, delayed afterdepolarizations, and triggered activity. Mechanical abnormalities including increased resting tension and aftercontractions, presumably resulting from intracellular Ca2+ overload, were produced by the hydroperoxides. Pretreatment with butylated hydroxytoluene, an antioxidant, significantly inhibited the hydroperoxide-induced electrophysiological derangements and MDA accumulation in the myocardium. These results suggest that lipid peroxidation of membranes causes various electrophysiological and mechanical abnormalities and may play a role in the genesis of reperfusion-induced arrhythmias.