CHRONIC EFFECTS OF ORAL PROSTACYCLIN ANALOG ON THROMBOXANE A(2) AND PROSTACYCLIN METABOLITES IN PULMONARY-HYPERTENSION

Abnormal biosynthesis of thromboxane and prostacyclin has been implica ted in patients with primary pulmonary hypertension and secondary pulm onary hypertension associated with congenital heart disease, and could be involved in the pathogenesis of pulmonary vascular disease. The ch ronic effects of an oral prostacyclin analogue, beraprost sodium, on t hromboxane and prostacyclin biosynthesis and on pulmonary circulation were investigated in 15 children with pulmonary hypertension. The plas ma concentrations of thromboxane B-2 and 6-keto-prostaglandin F-1 alph a were measured, as was the urinary excretion of 11-dehydrothromboxane B-2 and 2,3-dinor-6-keto-prostaglandin F-1 alpha, which are stable me tabolites of thromboxane A(2) and prostacyclin, respectively. In patie nts with pulmonary hypertension, the plasma concentration of thromboxa ne B-2 and the ratio of thromboxane B-2 to 6-keto-prostaglandin F-1 al pha were greater than in healthy controls: 210 +/- 49 versus 28 +/- 4 pg/mL (P < 0.05) and 32.6 +/- 8.9 versus 5.7 +/- 1.8 (P < 0.01), respe ctively. After 3 months of administration of beraprost, the plasma con centration of thromboxane B-2 and the ratio of thromboxane B-2 to 6-ke to-prostaglandin F-1 alpha were reduced significantly: 210 +/- 49 to 9 8 +/- 26 pg/mL (P < 0.01) and 32.6 +/- 8.9 to 18.0 +/- 6.7 (P < 0.05), respectively. In contrast, the plasma concentrations of 6-keto-prosta glandin F-1 alpha in patients were slightly but not significantly high er than in controls, and did net change significantly after administra tion of beraprost. The concentrations of 11-dehydro-thromboxane B-2 an d 2,3-dinor-6-keto-prostaglandin F-1 alpha in urine correlated signifi cantly with thromboxane B-2 and 6-keto-prostaglandin F-1 alpha, respec tively, in plasma. Beraprost improved the imbalance of thromboxane and prostacyclin biosynthesis and has a potential efficacy for preventing the progressive development of pathological changes in pulmonary vasc ulature.