Toxic effects of ouabain on Purkinje fibers and ventricular muscle fibers

Abstract

Toxic effects of ouabain on single Purkinje fibers and ventricular muscle fibers were investigated in vitro by microelectrode technique. Toxicity developed much earlier in the specialized conducting fibers and consisted of a progressively increasing rate of diastolic depolarization and a decrease of amplitude and duration of the action potential. The majority of Purkinje fiber preparations developed extrasystoles and rapid spontaneous rhythms. The resting potential was much decreased. The ouabain-induced changes in ventricular muscle fibers occurred much later than did changes in Purkinje fibers and consisted of a decrease in the plateau and in the amplitude of the action and resting potential. Spontaneous depolarization was not observed in muscle fibers. The effect of the rate of stimulation on the development of ouabain toxicity was studied in another series of experiments on driven and quiescent muscles. Signs of toxicity appeared earlier in the driven muscles than in duplicate quiescent muscles and, at faster rates of stimulation, the time required for the toxic changes was shortened.

Voltage‐clamp studies of transient inward current and mechanical oscillations induced by ouabain in ferret papillary muscle

“…Nevertheless, it appears likely that in normal hearts, digitalis arrhythmias probably arise in Purkinje cells because this tissue is more sensitive than ventricular tissue (Vassalle, Karis & Hoffman, 1962;Somberg, Barry & Smith, 1981). On the other hand, digitalis is often used after myocardial infarctions and in other conditions in which the heart is not normal.…”

Correlation between Effects of Ouabain on the Canine Electrocardiogram and Transmembrane Potentials of Isolated Purkinje Fibers

“…However, there is evidence to suggest that the likelihood of digitalis-induced automaticity is increased in diseased hearts,13 when cardiac rate prior to toxicity has been rapid,2 a and in the presence of hypokalemia.14 Microelectrode studies on the electrophysiologic properties of single cardiac cells have frequently shown an increase in action potential duration at low rates of stimulation with lower drug concentrations or short periods of exposure.5' 6 With higher concentrations or longer periods of exposure decreases in action potential amplitude, resting membrane potential, plateau, and action potential duration have also been described.7' 8 Automaticity of cells in the specialized conducting system may be increased by high concentrations of digitalis glycosides especially in the presence of lower extracellular potassium concentrations'0 or faster stimulus rates. 7 In an attempt to correlate the effects of digitalis on the electrocardiogram of intact dogs with changes in the electrophysiologic properties of single cells of the ventricular conducting system, we conducted a series of experiments in which isolated preparations of cardiac Purkinje fibers were perfused with arterial blood from a donor dog. The ECG was recorded from the donor, transmembrane potentials were recorded from the isolated fibers, and digitalis was administered to the donor by intravenous injection.…”

Interactions of ouabain and noradrenaline in isolated rabbit's atria

“…Effective inactivation of the Na+-carrying system at the end of depolarization is suggested to account for the change in the early repolarization in Na+-poor solutions (Toda, 1968). An acceleration of repolarization induced by ouabain is also observed in atrial (Sleator, Furchgott, Guibareff & Krespi, 1964), ventricular (Stutz, Feigelson, Emerson & Bing, 1954;Vassalle, Karis & Hoffman, 1962) and Purkinje fibres (Kassebaum, 1963). This change is suggested to result from the increased K+ conductance.…”