Comparison of the chronotropic responses to local anesthetics (procaine, lidocaine, prilocaine, mepivacaine and bupivacaine) of the canine sinus node in situ.

Effects of local anesthetics (procaine, lidocaine, prilocaine, mepivacaine and bupivacaine) on the sinus node of the nerve-intact dog heart were studied in situ by means of selective perfusion of the sinus node through the sinus node artery. The agents caused a dose-dependent decrease in heart rate and the order of their potency in decreasing the heart rate was as follows, bupivacaine greater than lidocaine=mepivacaine=prilocaine greater than procaine. The decrease in heart rate produced by these local anesthetics was not affected by prior administration of atropine. With procaine and prilocaine, the decrease in heart rate was followed by an increase which was inhibited by propranolol given into the sinus node artery or was suppressed in reserpine-pretreated dogs. Tetrodotoxin also prevented the positive chronotropic effect of procaine. From these results the following conclusion can be drawn: the negative chronotropic effects of these agents are induced mainly by a direct inhibitory action on the sinus node, and partly by blockade of sympathetic tone, and the interaction with the postganglionic adrenergic nerves plays an important role in the induction of the positive chronotropic responses to procaine and prilocaine.