BIOSYNTHESIS OF PROSTACYCLIN AND THROMBOXANE A(2) DURING CHRONIC HYPOXEMIA IN CHILDREN WITH CYANOTIC CONGENITAL HEART-DISEASE

The high risk of vaso-occlusive events in children younger than 4 year s with cyanotic congenital heart disease and polycythaemia has been at tributed to increased thromboxane (Tx) A(2) formation. In older childr en with cyanotic congenital heart disease, however, the risk of vaso-o cclusive events is much lower. We therefore hypothesized that the form ation of TxA(2) and prostacyclin is not disturbed in this age group. W e measured urinary excretion of stable index metabolites of in vivo Tx A(2) and prostacyclin formation by gas chromatography-mass spectrometr y in nine children (age 5.9-14.4, median 8.7 years) with cyanotic cong enital heart disease, and in nine healthy, age-matched control subject s. The patients excreted less 2,3-dinor-TxB(2) (systemic TxA(2) format ion, P = 0.03), 2,3-dinor-6-keto-PGF(1 alpha) (systemic prostacyclin f ormation, P = 0.03) and TxB(2) (renal TxA(2) formation, P = 0.01) than the control subjects. We conclude that in children older than 5 years with cyanotic congenital heart disease, endogenous synthesis of TxA(2 ) and prostacyclin is not stimulated. This result may explain the lowe r risk of vaso-occlusive events in this age group as compared with you nger children. In addition, our results suggest that chronic hypoxaemi a may affect the in vivo formation of TxA(2) and prostacyclin and the metabolic disposition of TxB(2).