Hemodynamic effects of a constant intravenous infusion of piroximone in patients with severe congestive heart failure

The hemodynamic effects and serum levels of piroximone (MDL 19,205), a new inotropic agent with vasodilating properties, were measured in 10 patients with chronic severe congestive failure during a constant 48-h infusion. The initial five patients (group A) received piroximone at 10 μg/kg/min; however, because a sustained increase in heart rate ≥25% from baseline developed in two patients and an episode of paroxysmal supraventricular tachycardia developed in another, the last 5 patients (group B) received an 8 μg/kg/min infusion. Because the steady-state hemodynamic alterations of group A prior to the onset of tachyarrhythmias were similar to those of group B, these results were combined. A significant increase in cardiac output from 3.65 ± 0.31 (SE) to 5.20 ± 0.49 L/min and decrease in pulmonary capillary wedge pressure (27 ± 2 to 20 ± 2 mm Hg), right atrial pressure (18 ± 2 to 11 ± 2 mm Hg), and systemic vascular resistance (1811 ± 172 to 1293 ± 80 dynes · s · cm^-5) occurred (all p < 0.05) without a significant change in mean arterial pressure. The peak plasma piroximone level was lower in the eight patients who did not develop a sustained increase in heart rate ≥25% above baseline (2.1 ± 0.5 μg/ml; range 1.6-2.9 μg/ml) than in the two who did (5.0 and 5.8 μg/ml). The latter two patients had the highest serum creatinine levels in the study population. In conclusion, intravenous (i.v.) piroximone administered as a constant i.v. infusion produced favorable hemodynamic alterations in patients with chronic severe heart failure without untoward effects at an infusion rate of 8 μg/kg/min.