The acute hemodynamic effects of combining administration of digoxin (DIG)(0.01 mg/kg intravenously) with molsidomine (MLS)(4 mg sublingually) were compared with those of DIG and MLS considered alone in 12 patients with congestive heart failure following acute myocardial infarction. The patients were classified into two subgroups, A (cardiac index [CI] less than or equal to 2.2 L/min/m2 and B (CI greater than 2.2 L/min/m2), to verify differences between the responses to the three drug regimens. MLS significantly reduced systolic blood pressure from 121.2 +/- 12.3 (mean +/- SD) to 111.7 +/- 10.9 mm Hg (p less than 0.01) after 60 min, mean right atrial pressure (RAP) from 6.2 +/- 3.6 to 2.4 +/- 2.1 mm Hg (p less than 0.0001), mean pulmonary arterial pressure (PAP), left ventricular filling pressure (LVFP) from 20.6 +/- 2.1 to 12.2 +/- 2.8 mm Hg (p less than 0.0001), and pulmonary vascular resistance (PVR). Left ventricular stroke work index (LVSWI) significantly increased after 60 min. DIG induced a significant reduction in heart rate, RAP, PAP, and LVFP from 20.1 +/- 2 to 14.3 +/- 2.7 mm Hg (p less than 0.0001) after 90 min. Stroke volume index (SVI) increased from 24.7 +/- 4.2 to 27.7 +/- 3.1 ml/beat/m2 (p less than 0.001) and LVSWI from 25.9 +/- 7.2 to 31.9 +/- 5.4 g X m/m2 (p less than 0.0001). The combination of DIG and MLS produced a reduction in RAP, PAP, and LVFP greater than that achieved with either agent alone, with a further shift of the ventricular function curve to the left, thereby leading to an improvement in cardiac performance.(ABSTRACT TRUNCATED AT 250 WORDS)