Effects of ionic channel antagonists barium, cesium, and UL-FS-49 on vagal slowing of atrial rate in dogs.

In response to a brief vagal stimulus, the atrial rate initially slows, then transiently accelerates, and slows a second time. We determined the effects of three antagonists to two ionic channels on this characteristic triphasic pacemaker response. Brief bursts of vagal stimulation were delivered to anesthetized dogs, and atrial cycle lengths were recorded. Either barium, cesium, or UL-FS-49 was administered. Barium, which primarily blocks the acetylcholine-sensitive potassium current (IK,ACh), attenuated the initial vagally induced bradycardia by > 50% without affecting the subsequent acceleration or the secondary slowing. Cesium and UL-FS-49 [both of which primarily block the pacemaker current (If)] did not affect the initial vagal slowing of atrial rate but abolished the acceleratory portion of the response. The secondary slowing was abolished by cesium but not by UL-FS-49. We conclude that the initial rapid atrial response to acetylcholine is mediated mainly by the IK,ACh, with little contribution from the If. The subsequent acceleration is mediated by activation of the If.

Facilitated ventriculoatrial conduction: effects of sequential pacing interval and basic cycle length.

We studied 1) the effects of pacing interval, 2) the timing of atrioventricular sequential pacing, and 3) the effects of successive premature intervals on retrograde conduction of the atrioventricular (AV) node in open-chest alpha-chloralose-anesthetized dogs. The ventricles and atria were sequentially paced at one of three levels of basic cycle length and one of six sequential time intervals (V1-A1) for three basic cycles (V1-V1). Then a premature ventricular impulse was introduced at various V1-V2 intervals, and the resultant retrograde conduction time (V2-A2 interval) was measured. Successive V1-V2 intervals were applied in an incremental or a decremental fashion. The V1-V2 intervals ranged from V1-V1 to V1-V2, at which the retrograde conduction was blocked. For each level of the above three factors, we plotted retrograde conduction time (V2-A2) as a function of the various premature intervals (V1-V2). We found that the time between atrial and ventricular activations was the most important factor in determining V1-V2 and in decreasing the effective refractory period of the AV node during retrograde conduction.