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.