Mechanism of positive chronotropic response of the canine SA node to selective administration of ketamine.

Mechanism for induction of the positive chronotropic effect of ketamine was studied in vivo using a selective perfusion technique of the canine SA node artery. In the reserpinized dogs in which tyramine responsiveness could be restored with norepinephrine, an injection of ketamine induced no sinus acceleration, while its prior administration to norepinephrine suppressed the response to tyramine. In the tetrodotoxin treated preparation in which the effect of electrical stimulation of the vagus and the stellate ganglion was abolished, tyramine produced an increase of sinus rate as usual, but the induction of sinus tachycardia by cocaine and ketamine was completely blocked. The results indicated that the positive chronotropic response of the SA node to ketamine might be induced by an inhibition of the norepinephrine uptake at the adrenergic nerve endings in a cocaine-like manner.