Effect of Changes in Cycle Length on Diastolic Depolarization Produced by Ouabain in Canine Purkinje Fibers

Abstract

Isolated canine papillary muscle-false tendon tissue preparations stimulated at a cycle length of 630 msec were treated with ouabain (2.1 x 10 -7 M ) until an increase in the slope of diastolic depolarization of Purkinje fibers was produced. Then the effects of changes in cycle length on the slope were tested. Sustained shortening of the cycle length increased the slope, and sustained lengthening had the opposite effect. An abrupt decrease in cycle length caused by a stimulus during phase 3 of a driven beat induced an increase in the slope of diastolic depolarization for one or more subsequent cycles. This procedure occasionally led to the spontaneous generation of an action potential which propagated into surrounding tissue. Suspension of stimulation often was followed by spontaneous beats. Shortening of the cycle length decreased the time of onset and increased the number and frequency of spontaneous beats. These effects were correlated with increases in the slope of diastolic depolarization. The diastolic depolarization of Purkinje fibers in false tendons was increased earlier and to a greater degree by ouabain than was the depolarization of Purkinje fibers on the muscle surface. These findings suggest that enhancement of diastolic depolarization of Purkinje fibers to the point of spontaneous discharge of action potentials may be a common means by which digitalis produces a variety of ventricular arrhythmias observed in intact animals.

Oscillatory afterpotentials in dog ventricular muscle fibers.

“…It has been reported that premature excitations enhance the amplitude of the OAPs and sometimes cause triggered activity (Davis, 1973;Cranefield and Aronson, 1974;Wit and Cranefield, 1976). Therefore, we tested the effect of premature excitation on the OAPs and found that it caused an increase in amplitude of the OAPs (Fig.…”

“…Only since it has been suggested that they are important factors in digitalis-induced arrhythmias have these activities been studied in detail (Rosen et al, 1973;Davis, 1973;. OAPs induced by digitalis occur in Purkinje fibers, atrial specialized conducting tissues Hashimoto and Moe, 1973), and ventricular muscle fibers (Ferrier, 1976).…”

“…This is because oscillatory afterpotentials (OAPs) can induce triggered activity when they become large enough to attain threshold. The resultant triggered activity is not the result of reentry but, rather, is abnormal pacemaker activity, resulting from a mechanism other than normal pacemaker activity (Cranefield, 1975;Ferrier, 1977).OAPs have been observed in digitalis-poisoned Purkinje and atrial plateau fibers (Rosen et al, 1973;Davis, 1973;Hashimoto and Moe, 1973), in canine Purkinje fibers exposed to a Na + -free, Ca 2+ -rich solution (Cranefield and Aronson, 1974), in fibers of the simian mitral valve (Wit and Cranefield, 1977), and in rabbit right atrial fibers (Saito et al, 1978). The OAPs and triggered activity in these cases were associated with the specialized fibers of the heart, as well as with fibers depolarized to -60 mV or less.…”

Automaticity, triggered activity, and responses to adrenergic stimulation in cat subendocardial Purkinje fibers after healing of myocardial infarction.

“…The delayed afterdepolarizations and triggered activity observed in our study were similar to those noted in other preparations. 8 [23][24][25][26][27] The amplitude and coupling interval of delayed afterdepolarizations were a function of the cycle length and number of preceding impulses, and were dependent on extracellular Ca' + concentration (figures 5 to 7).…”

Actions of a newly synthesized compound (711389-S) on various types of experimentally induced arrhythmias in mammalian species in situ.

“…In relation to the genesis of ouabain-induced arrhythmias, oscillatory afterpotentials leading to triggered activity in cardiac Purkinje fibers are con sidered to play a major role (13)(14)(15)(16)(17); the mechanisms whereby the afterdepolarization occurs in the presence of cardiac glycosides could be explained by a hypothesis that the excess Na+ entry and/or accumulation of internal Na+ resulted from inhibition of Na-K ATPase by ouabain increase internal Ca2+ through altered Na-Ca exchange. An increase in internal Ca2+, then, would activate non specific inward currents, and the inward cur rent is responsible for the genesis of the transient afterdepolarization (16,18).…”