Increased levels of circulating adhesion molecules in neonates with congenital diaphragmatic hernia complicated by persistent pulmonary hypertension

Abstract

The aim of this study was to determine circulating levels of adhesion molecules in serum from patients with congenital diaphragmatic hernia (CDH) to investigate the relationship between soluble ICAM-1, ELAM-1, and VCAM-1 liberated by activated vascular endothelium and the development of persistent pulmonary hypertension (PPH) in patients with CDH. We measured serum levels of ICAM-1, ELAM-1, and VCAM-1 in 20 high-risk neonates with CDH at the time of diagnosis (11 with PPH and 9 without PPH) and 7 age-matched controls using ELISA system. We further examined the lungs of 5 patients with CDH complicated by PPH who died during resuscitation and stabilization, and three control lung specimens for the expression of adhesion molecules using immunohistochemistry. The mean serum ICAM-1 levels in CDH patients with PPH (227.0+/-98.9 ng/ml) were increased compared with levels in CDH patients without PPH (140.29+/-37.4 ng/ml; p<0.05) and controls (130.0+/-23.8 ng/ml; p<0.05). Mean serum ELAM-1 levels in CDH patients with PPH (116.5+/-19.2 ng/ml) were significantly increased compared with levels in CDH patients without PPH (79.3+/-27.9 ng/ml; p<0.01) and controls (58.4+/-14.5 ng/ml; p<0.001). Mean serum VCAM-1 levels in CDH patients with PPH (1596.9+/-460.4 ng/ml) were significantly higher compared with levels in CDH patients without PPH (1069.3+/-444.6 ng/ml; p<0.01) and controls (838.0+/-171.2 ng/ml; p<0.001). But serum adhesion molecule levels in CDH patients without PPH were no different from controls statistically. Pulmonary vascular endothelial cells from CDH lung with PPH had strong expression of adhesion molecules compared with controls. Up-regulated expression of adhesion molecules on the endothelium of pulmonary vessels and high circulating levels of adhesion molecules in CDH patients with PPH suggest that adhesion molecules may play a role in the development of PPH in CDH.