Differential effects of nitroglycerin, trimetazidine, verapamil and SK&F 24260 on venous return as revealed by the open-loop method in the dog.

Abstract

To obtain detailed information concerning the effects of different vasodilators on venous return, experiments were carried out on 28 dogs by the use of the open-loop method. Blood from the superior and inferior venae cavae was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant flow rate. Changes in reservoir volume reflected a total blood shift from the experimental dog and indicated changes in venous return. Drugs were administered into the ascending aorta. Nitroglycerin (1-10 micrograms/kg) decreased systemic blood pressure, total peripheral resistance and venous return but scarcely altered heart rate. Trimetazidine (0.3-3 mg/kg) decreased systemic blood pressure, total peripheral resistance, venous return and heart rate. Verapamil (10-100 micrograms/kg) decreased systemic blood pressure, total peripheral resistance and heart rate, and increased venous return. SK&F 24260 (1-10 micrograms/kg) decreased systemic blood pressure, total peripheral resistance and increased venous return. Only high doses (10-30 micrograms/kg) of SK&F 24260 reduced heart rate. Rigorous measurements of systemic output showed that nitroglycerin (10 micrograms/kg), trimetazidine (3 mg/kg), verapamil (100 micrograms/kg), SK&F 24260 ( 10 micrograms/kg) produced no change in this parameter. SK&F 24260 increased venous return even when sino-aortic baroreceptor reflex was eliminated, ruling out reflex venoconstriction as a possible cause of the increased venous return. The results suggest the following: [1] Vasodilators like SK&F 24260 and verapamil increase venous return by decreasing arterial and/or venous resistance. [2] If the effect which increases venous capacitance prevails over the effect which decreases arterial and/or venous resistance, venous return is reduced as is the case of nitroglycerin and trimetazidine.