Combination of positive inotropic and vasodilating substances in congestive heart failure

Summary Therapy combining vasodilators and inotropic agents is considered to be one of the most powerful means of improving cardiac function in patients with congestive heart failure (CHF). The vasodilators enhance the effectiveness of inotropic agents by providing a reduction in preload and/or afterload.Inotropic drugs with different mechanisms of action, such as digitalis glycosides, ephedrine, dopamine, dobutamine, ibopamine, terbutaline, salbutamol, pirbuterol, prenalterol, amrinone, and milrinone, have been tested in combination with vasodilators with a predominant effect on preload (nitrates, molsidomine), with a predominant effect on afterload (hydralazine, nifedipine), or with a balanced action on both arterial and venous beds (nitroprusside, prazosin, captopril), showing positive results.The problem of the combination of digitalis glycosides and vasodilators with different sites of action has been considered by our group. In 42 patients with CHF, digoxin (DIG, 0.01 mg/kg intravenously) was tested in combination with molsidomine (MLS, 4 mg sublingually) (12 patients), a nitrate-like agent with a predominant vasodilating action on the capacitance vessels, nifedipine (NFP, 10 mg sublingually) (22 patients), a Ca²⁺ antagonist drug with a predominant action on the resistance vessels, and captopril (CPT, 25 mg orally) (8 patients), an ACE inhibitor with a balanced effect on both preload and afterload. The combination DIG plus MLS caused a reduction in left ventricular filling pressure (LVFP) greater than that achieved with either agent alone. The hemodynamic improvement was obtained without side effects, in spite of the striking fall in preload. We stress that this investigation was performed on patients with CHF following acute myocardial infarction. The combination DIG plus NFP resulted in a higher output increase and a greater LVFP reduction when compared with DIG or NFP alone, indicating a shift to a more improved left ventricular function curve. The combination DIG plus CPT provoked a decrease in LVFP greater than that achieved with either agent alone, while the increase in cardiac index and stroke volume index was not significantly different from that obtained with DIG or CPT.The results obtained by the combination of digitalis and a vasodilator with a pronounced effect on the resistance vessels, such as NFP, appear to be more favorable, since the reduction in impedance to left ventricular ejection allows a better ventricular emptying, thus leading to an improved cardiac output.