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In blood-perfused isolated canine atrium preparations, single injections of dibutyryl cyclic AMP at a dose range of 1 to 30 mg were made into the cannulated sinus node artery. At doses above 3 mg, dibutyryl cyclic AMP induced a biphasic chronotropic and inotropic response; there was a slight and rapid negative chronotropic and inotropic response, followed by a long-lasting positive chronotropic and inotropic response. The induction of the positive effects was slow, and it took 4 to 8 min to reach a maximum response. These effects continued 20 to 60 min. The ratios of the positive inotropic effect/positive chronotropic effect were very similar to those induced by norepinephrine. In this study, it was confirmed that a large dose of dibutyryl cyclic AMP induced a positive chronotropic and inotropic effect on the canine atrium, and the possibility was discussed that cyclic AMP may be involved in the effects of beta-adrenergic amines on the pacemaker and contractile process of the heart.

Effects of dibutyryl cyclic AMP on sinus rate and atrial contractile force in the isolated atrium of the dog.