Abstract

Methylguanidine, in the dose range of 10 to 300 mg, uniformly causes a dose-related increase in heart rate when it is administered to the heart-lung preparation of the dog. At dosage levels of 100 mg or above, there is a delayed second rise in heart rate. Pharmacological evidence supports the conclusion that the positive chronotropic effects are due to the release of catecholamine, presumably norepinephrine, from cardiac stores in the adrenergic fibers. The present studies directly demonstrate that, concomitant with the first and with the second heart rate increase, there is a rise in the norepinephrine content of the coronary sinus blood. Although the initial catecholamine-releasing effect of methylguanidine appears to be analogous to that produced by indirectly acting sympathomimetic amines, the mechanism by which the delayed release of norepinephrine occurs is not known.