Transmembrane activity was recorded from canine false tendons bathed with Tyrode's solution at 37°C. Stimulus patterns provided a 3-second pause after every ten beats. Acetylstrophanthidin was infused at concentrations up to 2x10 -7 g/ml. One or two transient depolarizations (TDs) followed the last driven response of each series. The appearance of TDs was associated with depression of normal phase-4 depolarization. The peak of the earliest TD (TD-1) occurred at an interval approximately equal to the basic cycle length. The later TD (TD-2) occurred at about twice the basic cycle length. Coupling intervals were determined primarily by the last cycle length. The amplitude of TD-1 was maximal when the basic cycle length was 600 msec, but TD-2 continued to increase as the basic cycle length diminished further. The amplitude of both TDs increased with the number of beats in the train. Either or both could reach threshold and induce single extrasystoles or trains of extrasystoles. TDs could be induced to reach threshold after each driven response, resulting in sustained bigeminal rhythms with fixed coupling. Possibly TDs provide a mechanism for various clinically observed arrhythmias induced by cardiac glycosides.

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...