We compared the short-term hemodynamic effects of intravenous fructose 1,6-diphosphate (FDP) administration in patients with coronary artery disease. Hemodynamic measurements were performed before and after administration of FDP in two groups of patients: those with impaired left ventricular (LV) function, elevated LV end-diastolic pressures (LVEDP > or =12 mm Hg, n = 30), and those with normal LV function (LVEDP <12 mm Hg, n = 17). In those with impaired LV function, FDP induced a decrease in LVEDP from 22 +/- 1.31 to 16.73 +/- 1.46 mm Hg (p< 0.0001). The cardiac index increased (2.50 +/- 0.11 to 2.81 +/- 0.13 L/m2 [p < 0.0001]), as did the LV stroke work index (31.7 +/- 2.04 to 40.3 +/- 2.67 gm x m x m2 [p < 0.0001]). FDP induced no significant change in heart rate and mean aortic pressure. Pulmonary pressure and resistance declined (p<0.002 and p< 0.0001, respectively). Systemic vascular resistance decreased because of increased cardiac output and unchanged arterial pressure (p < 0.001). In those patients with normal baseline LVEDP (5.06 +/- 0.27 mm Hg), FDP decreased heart rate (p< 0.0001) and systemic and pulmonary resistance (p < 0.03 and p < 0.004, respectively), whereas LVEDP and mean aortic and pulmonary pressures remained unchanged. FDP moderately increased cardiac output (p < 0.05), stroke volume index, and LV stroke work index (p< 0.002 and p< 0.003, respectively). The observed improvement in LV function in those patients with elevated LV filling pressures is thought to be a result of an increased energy production by the Embden-Meyerhoff pathway and to act as a positive inotrope.