Chronotropic Effects of Vagal Stimulation and Acetylcholine on Certain Mammalian Hearts With Special Reference to the Mechanism of Vagal Escape

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Abstract
In guinea pigs, rabbits and dogs the ventricular rate recovers very abruptly after vagal stimulation. The period of recovery was used to demonstrate that the vagi liberated acetylcholine at an approx. constant rate at least for a duration of stimulation that exceeded the time for vagal escape. A frequently repeated stimulus of the vagi did not cause any sign of exhaustion of the nerve action in dogs, whereas the mechanism of guinea pigs in some cases was easily exhausted. After exhaustion the response could be restored by the admn. of eserine (physostigmine), epinephrine or norepinephrine. While vagal stimulation stopped the heart, constant injns. of even high concns. of acetylcholine did not do so. The reason for this difference has been discussed and it has been suggested that the nerve liberates acetylcholine intracellularly in highly sensitive places (S.A. node) which the injd. acetylcholine penetrates with difficulty. Earlier investigations showing a higher concn. of Na in the S. A. node compared with the surrounding tissue were confirmed by the use of radiosodium (Na24). During vagal escape this unequal distr. of Na tended to disappear, which was thought to be a sign of a simultaneous decrease of the high sensitivity of the node to acetylcholine. On the basis of these findings the mechanism for vagal escape has been discussed.

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