No abstract

Rapid drive of isolated pacemaker tissues from cats resulted in a post-drive depression followed by a late acceleration to supernormal rates of pacemaker activity. These effects were similar to those occurring after drive of the pacemaker in situ . Lower SA nodal pacemakers discharged more slowly and irregularly than did upper SA nodal pacemaker cells. They were more readily depressed by rapid imposed drive. The balance between depression and acceleration varied in different preparations. Drive at only slightly above the intrinsic rate resulted frequently in acceleration not preceded by depression. Within limits, the greater the frequency and duration of drive, the greater the intensity and duration of both the depression and the late acceleration. Prostigmin augmented and atropine reduced post-drive depression. Cocaine potentiated the late acceleration. Excess potassium reduced post-drive depression and, in concentrations used, caused some acceleration. Pacemaker cells could be driven less rapidly than could other SA nodal cells. Drive generally shifted pacemaker action to a distant site; the first post-drive propagated responses originated from other pacemaker cells and dominance by the original unit was reestablished slowly. Rapid drive reduced amplitudes of action potentials and prepotentials. It also raised threshold potentials and during the post-drive period the durations of pacemaker cell action potentials were temporarily prolonged. In some preparations membrane potentials remained at a subnormal value after drive. Subthreshold potentials occurred at a somewhat subnormal rhythm but gradually developed an effective amplitude. Conduction block was observed in isolated SA nodal tissue. This was augmented during the post-drive period of depression. This work lends support to the hypothesis 1 that dominating action by pacemaker cells influences the pacemaker activity in other potential pacemaker tissues.

The interactions between pacemakers, and the effects on pacemakers, of terminating imposed driving were studied in the in situ heart of anesthetized dogs. Following atrial fibrillation or termination of a fast drive imposed through an artificial pacemaker, pacemaker action in intrinsic pacemakers is suppressed. Pacemakers tend to accelerate and compete with imposed drives which exceed control rates by only a small percentage (10 to 15%). Arrhythmias may result if imposed drive is slower than or identical with intrinsic pacemaker rate. Post-drive depression of pacemakers and the resulting deceleration of the heart is followed normally by an overshoot or supranormal acceleration. The magnitudes and durations of depression and late acceleration are proportional, within limits, to the rate and duration of drive. Atrioventricular and ectopic atrial pacemakers are much more readily depressed than is the sinoatrial pacemaker. Furthermore, beats of ectopic origin are much more likely to occur while subsidiary pacemakers are recovering from post-drive depression. Augmentation of depression by Prostigmin, its diminution by atropine, and the potentiation of late acceleration by cocaine and its absence after reserpine or guanethidine pretreatment, indicate that acetylcholine and catecholamines are liberated by driving stimuli. Placement of the pacemaker over the sinoatrial node, or near to regions where nerve terminals are concentrated, results in the greatest post-drive effects. The fact that propagated action potentials cause depressions and accelerations subject to drug block or potentiation indicates that mediators are also released in the course of propagated activity. Since atropine does not completely block post-drive depression, it is thought that a potassium ion shift may be involved.