THE ACTIONS OF HISTAMINE ON THE MAMMALIAN HEART

Werner Flacke ¹, D. Atanackovi ¹, R. A. Gillis ¹, and M. H. Alper ¹

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The action of histamine was investigated in the heart-lung preparation of the dog. Low doses of histamine (0.1-10 mg), given as single injections into the venous inflow tubing, caused a) an increase in heart rate, b) a decrease in atrial pressures, c) a transient decrease followed by an increase in P-Q interval, d) an increase in airway pressure, and e) an increase in pulmonary arterial pressure. Coronary sinus outflow was increased markedly by histamine. Antihistamine agents (promethazine, 3-10 mg; diphenhydramine, 3-10 mg) blocked completely the slowing of atrio-ventricular impulse conduction and the effects on pulmonary arterial pressure and airway resistance. They attenuated but did not block the effects on heart rate and contractility. High doses of histamine (30-300 mg) caused a slow, dose-dependent increase in heart rate and decrease in atrial pressure which was absent in hearts from dogs pretreated with reserpine and was antagonized by the beta-adrenergic blocking agent, propranolol. Before such high doses of histamine, there was a net uptake of norepinephrine, measured in arterial and coronary venous blood by the trihydroxyindole method, by the heart muscle; after histamine (300 mg) there was a massive net release of norepinephrine from the heart. The interaction between the two amines might play a role in physiologic or pathologic conditions involving massive release of histamine.

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