Fade of cardiac responses during tonic vagal stimulation.

We applied trains of stimuli to the vagosympathetic trunks of anesthetized dogs and studied the time courses of the resultant chronotropic and inotropic responses. These responses were maximum soon after the onset of the test stimulus train but then declined over the next 1-5 min despite continued stimulation. The fade ratio was defined as the magnitude of this decline divided by the magnitude of the maximum response. For both inotropic and chronotropic responses, maximum increased with stimulation frequency, but the fade ratio did not change. In some experiments, conditioning stimulus trains of variable duration were applied before a standard rest period, after which the test stimulus train was applied. The longer the conditioning period, the lower was the subsequent fade ratio of the inotropic responses to the test stimulation train. In other experiments, a conditioning train of 2 min was applied, and then variable rest periods were interposed before the test train was applied. The longer the rest period, the greater were the subsequent maximum and fade ratios of the inotropic responses to the test stimulus train. These results indicate that some factor persists well after the cardiac responses to a given stimulus, and this factor affects the next response to an identical vagal stimulation. The chronotropic responses faded about three times faster than the inotropic responses. Thus different mechanisms may account for the fade of the inotropic and chronotropic responses.