Electrophysiological derangements induced by lipid peroxidation in cardiac tissue.
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.
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
H
H
Nakaya
N
N
Tohse
M
M
Kanno
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D001555:Benzene Derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D004562:Electrocardiography; D004594:Electrophysiology; D005609:Free Radicals; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D008054:Lipid Peroxides / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010545:Peroxides / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D001555:Benzene Derivatives; D005609:Free Radicals; D008054:Lipid Peroxides; D008563:Membrane Lipids; D010545:Peroxides; D020122:tert-Butylhydroperoxide; C007164:cumene hydroperoxide