Hemodynamic and neurohumoral effects of long-term prostaglandin E1 infusions in outpatients with severe congestive heart failure

Abstract

Background: Prostaglandins of the E type are potent endogenous vasodilators that also interfere with the activity of the sympathetic nervous system. Thus treating patients with end-stage heart failure with prostaglandin E1 (PGE1) infusions seems to accord well with the hypothesis that neurohumoral imbalance rather than hemodynamic derangements should be the priority in the treatment of heart failure.

Methods: We sought to investigate neurohumoral in addition to hemodynamic changes during long-term PGE1 infusion and determined plasma renin activity, atrial natriuretic peptide, norepinephrine, and big endothelin plasma levels in 13 male patients with heart failure whose symptoms remained severe in spite of optimized oral therapy with digitalis, nitrates, furosemide (185 +/- 72 mg/d) and enalapril (33 +/- 3 mg/d). PGE1 infusion rate was started with 2.5 ng/kg/min and stepwise increased to the maximum tolerated dose (26 +/- 4 ng/kg/min), which was halved for continuous infusion through the following 12 hours and further stepwise reduced to an average dose of 8 +/- 1 ng/kg/min. Right heart catheterization was performed for acute hemodynamic studies and after 4 weeks. All patients were discharged with a catheter that was connected to a portable pump for home therapy.

Results: Acute effects of PGE1 were reductions in systemic blood pressure, (p < 0.05), right atrial pressure (p < 0.001), pulmonary artery pressure (p < 0.05), pulmonary capillary wedge pressure (p < 0.01), systemic and pulmonary vascular resistance index (both p < 0.01) and an increase in cardiac and stroke volume index (both p < 0.001) without a change in heart rate. After 4 weeks a persistent increase from baseline in cardiac index (from 1.9 +/- 0.1 to 2.5 +/- 0.2 L/min/m2; p < 0.01) and in pulmonary vascular resistance index (from 479 +/- 50 to 331 +/- 29 dynes x sec/cm5 x m2; p < 0.05) was observed. Atrial natriuretic peptide (p < 0.05) decreased, and norepinephrine and big endothelin showed a tendency to a lower level. Concomitantly, New York Heart Association functional class changed (p = 0.0001), with one patient's condition remaining class IV, the conditions of seven patients decreasing to class II, and the conditions of five patients decreasing to class III.

Conclusion: Thus long-term parenteral home therapy with PGE1 infusions in patients with severe end-stage heart failure elicited beneficial clinical and hemodynamic effects without activating neurohumoral counterregulatory systems.