Mechanisms of beneficial effects of vasodilators and inotropic stimulation in the experimental failing ischemic heart.

Both vasodilator and inotropic agents improve cardiac function in ischemic heart failure. However, since vasodilators may reduce coronary perfusion pressure and inotropic interventions may increase myocardial oxygen consumption (MVO2), both may increase myocardial ischemia. Accordingly, we determined myocardial blood flow and MVO2 in a canine model of failure induced by propranolol and volume load combined with acute coronary ligation. Both nitroprusside and digitalis reduced ventricular diastolic pressure (LVDP) and increased myocardial blood flow in the ischemic subendocardium. Decreased systolic wall tension also caused a significant reduction MVO2. The benefit of nitroprusside in failing hearts was obtained even with the addition of critical obstruction of the main left coronary artery (LCA). The role of preload reduction is emphasized by the contrasting results with nitroprusside in hearts with low LVDP: (1) decreased myocardial blood flow in ischemic subendocardium, and (2) left ventricular decompensation in animals with critical LCA obstruction. Thus, reduction of LVDP, which decreases subendocardial ischemia, is essential for the beneficial effects of vasodilators and inotropic interventions in ischemic heart failure. Decreased MVO2 caused by reduced heart size may also have a salutary role.