Cardiovascular responses to a newly developed cardiotonic agent, ZSY-39 [4-methyl-5-(4-pyridinyl)-thiazole-2-carboxyamide] in dog cross-circulated atrial and ventricular preparations.
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 30-1,000 micrograms/kg. At the same time, slight positive chronotropic and inotropic responses appeared in isolated, perfused atria at i.v. doses of 300 and 1,000 micrograms/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 300 micrograms). 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.
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003427:Cross Circulation; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010227:Parabiosis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D013844:Thiazoles; C053030:4-methyl-5-(4-pyridinyl)thiazole-2-carboxamide