Phasic effects of repetitive vagal stimulation on atrial contraction

The vagus nerves of anesthetized dogs were stimulated once each cardiac cycle with a brief burst of pulses, and the timing of the stimulus bursts was changed by a fixed increment on successive cardiac cycles. The effects of such vagal stimulation on atrial contraction depended on the number of pulses per stimulus burst, on the interval between pulses within the burst, and on the timing of the stimulus bursts within the cardiac cycle. The vagal stimulus bursts had the least negative inotropic effect when they were given less than 100 msec before the next atrial depolarization, and they were most effective when given about 330 msec before the next atrial depolarization. This dependence of the inotropic response on the timing of the vagal activity within the cardiac cycle indicates that the following conditions must prevail with respect to the vagal innervation of the atrium: (1) the acetylcholine released from the vagal nerve endings is hydrolyzed at a critically rapid rate in the atrial tissues, (2) the neurally released acetylcholine must exert its major influence on atrial contraction during some preferential fraction of the cardiac cycle (presumably, during depolarization), and (3) after a vagal stimulus of a given strength, the concentration of acetylcholine in the region of the myocardial cells will attain its maximum value during this critical phase of the cardiac cycle when the vagal stimuli are given at the optimal time in the cardiac cycle.