Matrix Metalloproteinase-9 Expression in Congenital Diaphragmatic Hernia During Mechanical Ventilation

Abstract

Matrix metalloproteinase-9 (MMP-9) is detected in lung tissues subjected to ventilator-induced injury and is involved in the process of lung injury. We investigated the immunohistochemical expression of MMP-9 in the bilateral lungs of newborns with congenital diaphragmatic hernia (CDH) during mechanical ventilation and evaluated the degree of damage based on MMP-9 expression. Lung tissue samples were obtained during autopsy from six newborns with CDH. Control lung tissue samples were obtained from two of these newborns; one who died of persistent pulmonary hypertension after being ventilated for 2 days, but whose bilateral lungs were not subjected to the compressions of herniation, and one who died of bilateral diaphragmatic hernias soon after birth, but was not subjected to artificial ventilation. The other four newborns with CDH had unilateral Bochdalek hernias. Immunohistochemical detection of MMP-9 expression was done using a wet autoclave antigen retrieval method on sections from formalin-fixed and paraffin-embedded lung tissue. The reaction and distribution of MMP-9 was strongly positive in the alveolar macrophages in thickened alveolar septi and ducts, and in the inflammatory cells around the parenchymal hemorrhage and intra-alveolar spaces. Only the four patients with unilateral Bochdalek hernia had widely positive MMP-9 immunoreactivity in the unaffected side, as well as the affected side. Based on MMP-9 expression, the lungs of newborns with CDH were damaged bilaterally during mechanical ventilation.