Effect of changes in cycle length on diastolic depolarization produced by ouabain in canine Purkinje fibers.

Isolated canine papillary muscle-false tendon tissue preparations stimulated at a cycle length of 630 msec were treated with ouabain (2.1 X ICHM) 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.