THROMBOXANE-A(2) AND PROSTACYCLIN BIOSYNTHESIS IN CHILDREN AND ADOLESCENTS WITH PULMONARY VASCULAR-DISEASE

Background. The pathogenesis of pulmonary vascular disease in children with congenital heart disease is incompletely understood. Thromboxane (TX) A2 and prostacyclin (PGI2) have opposing effects on platelet agg regation and pulmonary vascular smooth muscle. An imbalance in their b iosynthesis could contribute to the progressive increase in pulmonary vascular resistance seen in older untreated patients with pulmonary hy pertensive congenital heart disease and the thrombotic complications t hey may develop. Methods and Results. We investigated TXA2 and PGI2 bi osynthesis in 15 young children (0.2 to 2.25 years old) with congenita l heart disease with increased pulmonary blood flow and potentially re versible pulmonary vascular disease by measuring urinary excretion of 2,3-dinor-TXB2 and 2,3-dinor-6-oxo-prostaglandin (PG) F1alpha and comp ared the findings with those in 16 healthy children (0.5 to 2.8 years old). 2,3-Dinor-TXB2 excretion was greater in the patients than in con trol subjects (1253+/-161 versus 592+/-122 ng/g creatinine; P<.001). E xcretion of 2,3-dinor-6-oxo-PGF1alpha was 452+/-54 compared with 589+/ -95 ng/g creatinine in control subjects. In 5 patients who underwent s uccessful cardiac surgery greater-than-or-equal-to 1 year later excret ion of 2,3-dinor-TXB2 decreased from 1100+/-298 to 609+/-131 ng/g crea tinine (P<.05), a value comparable to those in 5 healthy children of s imilar age (749+/-226 ng/g creatinine). We also compared 15 patients ( 11 to 23 years old) with advanced irreversible pulmonary vascular dise ase with 19 healthy control subjects (10 to 23 years old). The ratio o f TX to PGI2 metabolite excretion was greater in the patients than in control subjects (3.5+/-0.6 versus 2.0+/-0.3; P<.05). Conclusions. The re is increased 2,3-dinor-TXB2 excretion in children with congenital h eart disease and a high pulmonary blood flow that may reflect an imbal ance in biosynthesis of TXA2 and PGI2 in the pulmonary vascular bed. T he imbalance may contribute to the progressive development of increase d pulmonary vascular resistance and persists in older patients whose h eart defects are uncorrected.