Effects of prostacyclin on the pulmonary vascular tone and cardiac contractility of patients with pulmonary hypertension secondary to end-stage heart failure

Long-term administration of prostacyclin (PGI(2)) improves the hemodynamic state, symptoms, and survival in patients with primary pulmonary hypertension, but it Increases mortality in patients with heart failure despite obvious hemodynamic benefits when it is given acutely. We evaluated the mechanisms of action of PGI(2) in patients with heart failure and secondary pulmonary hypertension. Nineteen patients with end-stage heart failure and pulmonary hypertension all candidates for heart transplantation, underwent right- and left sided cardiac catheterization with micromanometer-tipped catheters and were tested for PGI(2) at incremental doses. PGI(2) infusion significantly improved pulmonary hemodynamics with a 47% reduction in pulmonary vascular resistance (p = 0.0003) and a doubling of pulmonary artery compliance (p <0.0001), reflecting improvement in pulmonary vascular tone. The dose of PGI(2) necessary to reach this hemodynamic effect correlated significantly to the baseline severity of pulmonary artery compliance (r = 0.54, p = 0.01). Furthermore, PGI(2) produced a significant positive inotropic effect (contractile element maximum velocity increased from 1.10 +/- 0.09 to 1.33 +/- 0.13 circ/s, p <0.009). The hemodynamic effects of PGI(2) infusion were independent of the plasma and urinary levels of endogen prostaglandins. Thus, PGI(2) at therapeutic doses exerts a positive inatropic effect in patients with heart failure, which may explain the increased mortality rate observed with the long-term use of PGI(2) in this type of patient. The spectacular acute benefits on right ventricular afterload, however, may be useful in unstable patients with heart failure and secondary pulmonary hypertension or in transplanted patients with acute right ventricular failure of the donor heart. (C) 1998 by Excerpta Medica, Inc.