Basic and clinical studies on bay a 1040 with special reference to its influence on the coronary, systemic resistance and capacitance blood vessels

A series of basic and clinical studies on a new Antianginal agent, Bay a 1040, revealed the following facts. 1. With the artificial perfusion of a large branch of the coronary artery under a constant pressure head in closed-chest dogs, and with intracoronary injection as a bolus of 0.1 ml, 1.0 μg of Bay a 1040 produced a transient and minimal decrease in the mean coronary resistance to flow without any change in blood pressures. With 5 μg/kg injected intravenously, the mean resistance to flow decreased in the coronary area that was not exposed to the circulating Bay a 1040. From these observations it is probable that Bay a 1040 produces a mild “active” coronary dilatation as well as “passive” coronary dilatation. 2. With 5 μg/kg injected intravenously in open-chest dogs, the evoked circulatory change was that of transient dilatation of the systemic resistance vessels without any change in the capacitance of the circulatory system. 3. Middle-aged patients with ischemic heart disease responded to the oral administration of 20 mg with “dilatation” of the systemic resistance vessels. Left ventricular external work and pressure-time-product were also diminished. 4. A clinical trial with cross-over design revealed an outstanding. “preventive” efficacy of this agent, as given in daily dose of 60 mg in 3 divided portions, on the occurrence of anginal attacks in the patients with ischemic heart disease.