Abstract
The cardiovascular effects of ZSY-39 [4-methyl-5-(4-pyridinyl)-thiazole-2-carboxyamide] were investigated in isolated and blood-perfused atrial and ventricular muscles perfused with donor's arterial blood. When ZSY-39 was given i.v. to the intact donor dog, hypotension with a slight tachycardia was induced at a dose range of 30-1, 000μg/kg. At the same time, slight positive chronotropic and inotropic responses appeared in isolated, perfused atria at i.v. doses of 300 and 1, 000μg/kg ZSY-39, indicating a relatively dominant inotropic action.
Direct injection of ZSY-39 into the cannulated sinus node artery of the isolated atrium produced positive chronotropic and inotropic responses in a dose-related manner (1 to 300μg). ZSY-39 also induced a dose-dependent increase in developed tension in the isolated ventricle. The positive chronotropic and inotropic effects of ZSY-39 were not modified by an adequate dose of propranolol which completely blocked norepinephrine-induced positive chronotropic and inotropic responses. From these results, it is concluded that ZSY-39 has mild cardiotonic properties, showing relatively selective positive inotropic activity.