Conduction Block Associated with Transient Depolarizations Induced by Acetylstrophanthidin in Isolated Canine Purkinje Fibers

Abstract

Transient depolarizations (TDs) appeared in canine Purkinje tissue but not in cardiac muscle during exposure to 1-2 X 10~7 g/ml of acetylstrophanthidin. At low levels of toxicity, the TDs were associated with a decrease in threshold and an increase in automaticity. As intoxication progressed, the TDs coincided with transient periods of increased threshold and conduction block. Propagation from muscle to Purkinje tissue was blocked during, but not before or after, the crest of the TDs. As a result of the interaction between temporal and spatial (electrotonic) factors, various patterns of block, including unidirectional block, were observed. At moderate frequencies 2:1 block was demonstrated, but at faster rates 1:1 transmission occurred. At a later stage of toxicity, repetitive stimulation led to progressive depolarization in Purkinje tissue followed by a period of block during which slow repolarization eventually restored excitability and conductivity. In the whole heart, conduction block could permit reentry and could be responsible for the ultimate transition from ventricular tachycardia to ventricular fibrillation. KEY WORDScardiac glycosides decremental conduction threshold Purkinje-muscle junction unidirectional block reentry• Automaticity and intraventricular block are important features of digitalis intoxication. Idioventricular rhythms occurring in the intact animal are commonly attributed to enhanced phase-4 depolarization and depressed conductivity, particularly in the specialized conducting tissue of the ventricles (1.2). In a study of the mechanisms of acetylstrophanthidin toxicity in isolated canine Purkinje-papillary muscle preparations (3), we have observed transient depolarizations (TDs) of the transmembrane potential. The TDs appear as one or two phasic oscillations of the membrane potential coupled to the last of a series of driven responses with a period approximately equal to the preceding cycle length. Although different from phase-4 depolarization, the TDs can reach threshold, and cause one or more From the Masonic Medical Research Laboratory, Utica, New York 13501.This study was supported in part by the American Heart Association and the Heart Association of Upstate New York, Syracuse. Dr. Saunders was supported by a training grant from the National Heart and Lung Institute to the Department of Medicine, Upstate Medical Center, Syracuse. Dr. Ferrier was a Postdoctoral Fellow of the Canadian Heart Foundation, 1970-1972. Dr. Saunders's present address is Department of Medicine, University of Utah, Salt Lake City, Utah 84112.Received October 30, 1972. Accepted for publication March 15, 1973. automatic responses; moreover, they are probably responsible for the repetitive ventricular responses described by Lown et al. (4) and Klein et al. (5) and the postpacing acceleration described by Gandel et al. (6). Under certain conditions, TDs can also cause conduction block in isolated preparations. Although there are at present no experimental or clinical correlates of this type of blo...

Transient Depolarizations Induced by Acetylstrophanthidin in Specialized Tissue of Dog Atrium and Ventricle

“…If we assume that the functional connections are of low internal resistance, it follows that the electrotonic influence of the muscle fibers would restrain, retard, or prevent the development of automatic activity in the attached plateau fibers. Comparable phenomena have been described in ventricular preparations of false tendons attached to papillary muscle or ventricular free wall (2). TDs are regularly of greater amplitude in Purkinje tissue remote from muscle and decrease progressively as muscle is approached.…”

“…• Isolated preparations of Purkinje tissue excised from dog ventricles exhibit transient depolarizations (TDs) when they are exposed to moderate concentrations of acetylstrophanthidin (1,2). The TDs, usually two sequential events, are frequency dependent: their coupling intervals and their amplitudes are direct functions of the preceding cycle length.…”

Overview of Basic Mechanisms of Cardiac Arrhythmia

“…DADs and DAD-induced triggered activity are observed under conditions that augment intracellular calcium, [Ca 2+ ] i , such as after exposure to toxic levels of cardiac glycosides (digitalis) 36–38 or catecholamines. 30,39,40 This activity is also manifest in hypertrophied and failing hearts 41,42 as well as in Purkinje fibers surviving myocardial infarction.…”

Effects of tetrodotoxin, lidocaine, verapamil, and AHR-2666 on Ouabain-induced delayed afterdepolarizations in canine Purkinje fibers.

“…They occur in Purkinje (Davis, 1973;Rosen et al, 1973aRosen et al, , 1973bSaunders et al, 1973) and atrial (Hashimoto and Moe, 1973;Hordof et al, 1978) specialized fibers after exposure to toxic concentrations of digitalis, and also in ventricular muscle (Ferrier, 1976). At the time of their occurrence in previously normal fibers, the transmembrane resting potential usually has decreased by approximately 10 mV.…”