Combined vasodilator and inotropic therapy of heart failure: Experimental and clinical concepts

Vasodilators facilitate ventricular emptying by affording earlier onset of left ventricular (LV) ejection and increased stroke volume with achievement of a reduced end-systolic pressure and volume. Agents with positive inotropic properties increase stroke volume by shifting the end-systolic pressure-volume curve to the left through augmented force and velocity of contraction. With impedence reduction, improvement in pump performance occurs concomitant with reduced cardiac energy requirements (MVO₂); positive inotropic agents under most circumstances increase MVO₂. The combination of a vasodilator and positive inotropic agent, as opposed to either alone, in the conscious animal shifts to the left and increases the slope of the LV end-systolic pressure-volume relation. Cardiac efficiency, defined by the slope of the relation between stroke volume and systolic tension, is increased by the combination of the drugs. In clinical heart fallure, nitroprusside alone lowers LV preload with a modest increase in cardiac output (CO); dopamine markedly increases CO with little fall in LV preload. In combination the two agents achieve the individual beneficial effects of each drug, and cardiac efficiency indices are improved. Thus combined vasodilator and inotropic therapy appears to have a sound physiologic rationale and clinically documented beneficial effect superior to either modality alone.