Mechanisms underlying early development of pulmonary vascular obstructive disease in Down syndrome: An imbalance in biosynthesis of thromboxane A 2 and prostacyclin

Patients with Down syndrome (DS) and a left‐to‐right shunt often develop early severe pulmonary hypertension (PH) and pulmonary vascular obstructive disease (PVOD); the pathophysiological mechanisms underlying the development of these complications are yet to be determined. To investigate the mechanisms, we evaluated the biosynthesis of thromboxane (TX) A 2 and prostacyclin (PGI 2 ) in four groups of infants, cross‐classified as shown below, by measuring the urinary excretion levels of 11‐dehydro‐TXB 2 and 2,3‐dinor‐6‐keto‐PGF 1α : DS infants with a left‐to‐right shunt and PH (D‐PH, n = 18), DS infants without congenital heart defect (D‐C, n = 8), non‐DS infants with a left‐to‐right shunt and PH (ND‐PH, n = 12), and non‐DS infants without congenital heart defect (ND‐C, n = 22). The urinary excretion ratios of 11‐dehydro‐TXB 2 to 2,3‐dinor‐6‐keto‐PGF 1α in the D‐PH, D‐C, ND‐PH, and ND‐C groups were 7.69, 4.71, 2.10, and 2.27, respectively. The ratio of 11‐dehydro‐TXB 2 to 2,3‐dinor‐6‐keto‐PGF 1α was higher in the presence of DS ( P  < 0.001), independently of the presence of PH ( P  = 0.297). The predominant biosynthesis of TXA 2 over PGI 2 , leading to vasoconstriction, was observed in DS infants, irrespective of the presence/absence of PH. This imbalance in the biosynthesis of vasoactive eicosanoids may account for the rapid progression of PVOD in DS infants with a left‐to‐right shunt. © 2010 Wiley‐Liss, Inc.