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The fetal rat heart in organ culture was used to investigate rate chanes by various cardioactive agents. Concomitantly, the effect of these pharmacologically induced rate changes on steady-state cyclic adenosine monophosphate levels was determined. Isoproterenol increased the fetal rat heart rate and cyclic adenosine monophosphate in a concentration-related fashion. Quinidine produced a concentration-related decrease in heart rate and no change in cyclic adenosine monophosphate level. The dysrhythmogenic agent produced concentration-related negative chronotropism in the fetal rat heart preparation and significant elevations in cyclic adenosine monophosphate at concentrations without chronotropic action. No correlation between chronotropic effect of a drug and cyclic adenosine monophosphate levels was observed.

Dibutyryl cyclic AMP and cyclic AMP in a DMSO medium were administered to the fetal rat heart in organ culture. Changes in heart rate were observed. Dibutyryl cyclic AMP in concentrations of 5 X 10(-5) M and 1 X 10(-4) M produced significant negative chronotropism. At a concentration of 1 X 10(-3) M, cyclic AMP in a 3% or 0.5% DMSO medium produced significant negative chronotropism. These data were compared with other studies. The negative chronotropic action of cyclic AMP and its dibutyryl derivative are evidence against the involvement of cyclic AMP in positive cardiac chronotropism.

The fetal rat heart in organ culture was used to study the interaction of calcium with the cardioactive agents. McN-2165 is an agent that produces negative chronotropism and elevation in cyclic AMP levels in this preparation. A concentration of 2.76 mM calcium ion antagonized the negative chronotropic action and prevented the cyclic AMP elevation produced by this agent. Positive chronotropic actions of isoproterenol were prevented by decreasing the calcium level below 1.84 mM.