RATE-INCREASING ACTION OF METHYLGUANIDINE UPON THE ISOLATED MAMMALIAN HEART

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

Methylguanidine in the dose range of 10 to 300 mg, in the heart-lung preparation of the dog with a total blood volume of about 1 liter, uniformly causes an increase in heart rate. Higher doses do not further increase the rate. The effect is not modified by prior administration of hexamethonium (10 mg). It is slightly enhanced in the presence of atropine (10 mg of atropine sulfate) and markedly reduced in the presence of cocaine (6 mg). Reserpine pretreatment of the dogs (0.5 mg/kg of body weight either once at 24 hr or twice at 48 and 24 hr prior to isolation of the hearts) as a rule prevents the effect; in only one of seven experiments did a much reduced effect occur. The evidence supports the conclusion that the rate-increasing effect of methylguanidine is due to release of catecholamines, presumably norepinephrine, from cardiac stores in the adrenergic fibers. In its norepinephrine -releasing action in the heart-lung preparation, methylguanidine has approximately the effectiveness of reserpine, but (on a molar basis) only 1/8000 the potency. In the dosage range between 100 and 300 mg in the heart-lung preparation, methylguanidine causes an increase in pulmonary pressure, the nature of which has not been elucidated