Time-dependent heart period and contractility responses to successive brief vagal stimuli

The vagosympathetic trunks of anesthetized propranolized dogs were stimulated with brief electrical bursts, and heart period (P-P interval), atrioventricular conduction (P-R interval), and pressure generated on a balloon anchored in the atrium (AP) were measured. Two vagal stimulus bursts were given separated by an integral number of cardiac cycles but with each placed at the same relative time in the cardiac cycle. The time between stimulus bursts (T) varied from 2 to 60 s. For all cardiac variables over this time span, the peak response to the second stimulus (P2) was less than that of the first (P1) i.e., the ratio P2/P1 was less than unity. The maximum depression of P2/P1 for all variables occurred at a T of about 5 s. The effect of changing the time in the cardiac cycle at which the stimulus was given, and the effect of stimulus intensity on the P2/P1 ratio was also measured. Previous experiments observing the P-R interval alone suggested that synthesis and release of acetylcholine were not involved in the time dependent P2/P1 effect. The present results suggest that neuroeffector mechanisms at the target cellular level are also not involved in the depression of P2/P1. A time-dependent increase in acetylcholine inactivation is consistent with the present results, but an antagonism between primary and secondary inhibitory effects also cannot be ruled out.