Cardiac and systemic hemodynamic actions of the slow channel calcium blocking agent, KB-944.
The effects of KB-944 (10-400 micrograms/kg/min, i.v.), a new slow channel calcium blocking agent, on myocardial oxygen utilization, regional myocardial perfusion and hemodynamics were measured in anesthetized dogs. KB-944 produced significant dose-related increases in coronary blood flow and decreases in heart rate, left ventricular systolic pressure, aortic blood pressure and peripheral vascular resistance. At high doses, peak positive and negative dP/dt were both reduced and left ventricular end diastolic pressure increased. KB-944 reduced arterial-venous oxygen content difference across the heart while significantly increasing coronary blood flow. The pressure rate product, an index of myocardial oxygen consumption, was also reduced. KB-944 produced a uniform and dose-related increase in transmural tissue flow within the left ventricular free wall. These results indicate that KB-944, a new slow channel calcium blocking agent, is a potent peripheral and coronary vasodilator with negative inotropic and chronotropic properties and may be potentially useful in coronary artery disease or hypertension.
D000818:Animals; D052160:Benzothiazoles; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003971:Diastole / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D013599:Systole / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D052160:Benzothiazoles; D002121:Calcium Channel Blockers; D013844:Thiazoles; C035950:fosfedil