AJP - Heart and Circulatory Physiology, Vol 253, Issue 5 1089-H1097, Copyright © 1987 by American Physiological Society
Electrophysiological derangements induced by lipid peroxidation in cardiac tissue
H. Nakaya, N. Tohse and M. Kanno
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
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.
