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The isolated canine right atrium containing the S-A node area was perfused via the sinus node artery at a constant pressure of 100mm Hg with the blood from a donor dog by a cross-circulation technique. The selective administration of caffeine at doses of 100 μg to 1mg into the sinus node artery of the isolated right atrium always induced double peaked positive chronotropic responses, i.e., rapidly induced initial acceleration followed by slowly induced but long-lasting one. The initial positive response to caffeine was hardly suppressd by either adrenergic beta-blocking agents, H 56/28 (alprenolol) and propranolol, or tetrodotoxin. On the contrary, the secondary positive chronotropic response was effectively inhibited by either adrenergic beta-blocking agents or tetrodotoxin. These results suggest that caffeine-induced initial acceleration is not due to catecholamine while the secondary one is due to catecholamine which is released by excitation of local adrenergic fibers.

Double Peaked Positive Chronotropic Response of the Isolated Blood-perfused S-A Node to Caffeine