Continuous infusion of epoprostenol improves the net balance between pulmonary endothelin-1 clearance and release in primary pulmonary hypertension

Background-Primary pulmonary hypertension results from progressive narrowin g of the precapillary pulmonary vasculature. A variety of endothelial abnor malities have been identified, including a net reduction in pulmonary clear ance of the vasoconstrictor and smooth muscle mitogen endothelin-1, In many patients, net pulmonary release of endothelin-1 is observed. Chronic infus ions of epoprostenol (prostacyclin) improve functional capacity, survival, and hemodynamics in patients with advanced primary pulmonary hypertension. We hypothesized that the epoprostenol infusions, as compared with conventio nal therapy, might alter the abnormal pulmonary endothelin-1 homeostasis. Methods and Results-Using a subset of patients from a larger randomized stu dy comparing epoprostenol plus conventional therapy (n = 11 in the present study) with conventional therapy alone (n = 7 in the present study), we det ermined the ratio of plasma endothelin-1 levels in systemic arterial blood leaving the lung to levels in mixed venous blood entering the lung both bef ore randomization and after 88 days of continuous therapy. There were no di fferences between the 2 groups before therapy, but by day 88, the epoproste nol-treated group had a greater proportion of patients (82%) with an arteri al/venous ratio < 1 than did the conventional therapy group, in which only 29% of patients had a ratio < 1 (P < 0.05). Conclusions-These results suggest that continuous epoprostenol therapy may have a beneficial effect on the balance between endothelin-1 clearance and release in many patients with primary pulmonary hypertension and may provid e one explanation for the salutary effect of epoprostenol in this disease.