Role of fibrinolysis in development of hyaline membrane disease in newborn rabbits.

The role of fibrinolysis in the pathogenesis of hyaline membrane disease was studied in newborn rabbits at 28- or 29-day gestation. Hyaline membrane was recognized in the lungs of rabbits that were exposed to intrauterine hypoxia and received trans-4-aminomethylcyclohexane carboxylic acid (t-AMCHA), a plasmin inhibitor found to cause a marked decrease in the fibrinolytic activity of lung extracts. In the newborn rabbits subjected to intrauterine hypoxia alone, surface activity of lung extracts was reduced, but hyaline membrane was not seen. By immunofluorescent examination the hyaline membrane was found to be rich in fibrinogen and its derivatives. Electron microscopic examination revealed that they contained various amounts of cellular debris, bundles of fibrils and electron-dense, finely granular deposits and polymerized fibrin with 230 A periodicity. Disintegration of pulmonary epithelial cells was also seen. These findings indicate that diminished fibrinolytic activity of lung tissue contributes to intra-alveolar accumulation of fibrinogen, fibrin and their degradation products, thereby bringing about morphological and physiological disintegration of the terminal airways.