A pharmacologic analysis of chronotropic and inotropic responses to direct electrical stimulation of the isolated, blood-perfused canine atrium.

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Abstract
Electrical stimulation on the posterior portion in the caval margin of the right atrium caused a biphasic chronotropic and inotropic response, i.e., a negative response followed by a positive response, in the isolated blood-perfused canine atrial preparation. The threshold of pulse duration for inducing negative responses was approximately 0.05 ms at 2 v and 20 Hz, but that for inducing positive responses was approximately 0.5 ms. When the voltage and pulse duration of electrical stimulation were increased, both the degree of negative and positive responses became greater. Muscle contracture was frequently induced by increasing the voltage or pulse duration. The optimal frequency was 20-40 Hz for inducing marked chronotropic and inotropic responses. The negative chronotropic and inotropic response to subthreshold electrical stimulation was significantly suppressed by the treatment with tetrodotoxin, hexamethonium or atropine, while it was enhanced by physostigmine treatment. Subthreshold electrical stimulation readily caused a release of acetylcholine by excitation of parasympathetic preganglionic fibers in this atrial preparation. The positive chronotropic and inotropic response was significantly suppressed by treatment with propranolol and by tetrodotoxin, while it was enhanced by imipramine, hexamethonium or atropine. This blood-perfused preparation apparently is very suitable to evaluate both cardiac mechanisms controlled by autonomic nervous system and drug actions on effect of endogenous hormone.