Pharmacological Evidence for the Importance of Catecholamines in Cardiac Rhythmicity

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Abstract
Dogs with complete heart block were used to explore the dependence of the intrinsic rhythmicity of the heart on catecholamine activity. By the use of reserpine, hexamethonium, and surgical sympathectomy, it was demonstrated that, while reduction in catecholamine activity slows both the atrial and the ventricular rates, the ventricular pace maker was always affected to a greater degree. The effect of a combination of reserpine and hexamethonium on the ventricle was greater than when either agent was administered alone, suggesting that the greater the sympathetic blockade, the greater the depression in pacemaker rhythmicity. Since the course of its action on the heart paralleled that of catecholamine depletion, it seems probable that the effect of reserpine on rhythmicity was due to its catecholamine depleting action. It was thought unlikely that prolonged hypotension contributed to the reserpine action on the heart. It is indicated that disturbances in electrolyte balance and blood pH did not play a role in the effects observed.