ENHANCED PROCOAGULATORY ACTIVITY, HYALINE-MEMBRANE FORMATION AND SURFACTANT IMPAIRMENT IN BABOON BRONCHOALVEOLAR LAVAGE FLUID - STUDIES ON A NEW MODEL COMBINING ACID ASPIRATION AND OLEIC-ACID INFUSION

Intraalveolar induction of procoagulant activity and the subsequent fo rmation of hyaline membranes are typical findings in acute lung injury . To expand our knowledge on the time course of intraalveolar clotting disorders, we developed an experimental protocol and studied the chan ges in activity of factors possibly critical for fibrin deposition and their possible influence on surfactant activity. We created a model o f moderate acute lung injury by inflicting adult baboons with a combin ation of intratracheal acid aspiration and intravenous oleic acid infu sion. Hemodynamic, metabolic, and respiratory parameters were recorded . Bronchoalveolar lavage (BAL) was performed at several time points be fore, during, and after the 72 h observation period. Leukocyte activat ion and occurring inflammation are reflected by a persistent elevation of granulocyte-specific elastase throughout the experiment and a shar p increase in interleukin (IL)-6 at 8 h and at 24 h. Permeability incr ease and massive albumin influx into the alveolar space are characteri zed by the albumin BAL/plasma quotient increase. The induction of larg e amounts of thrombin-antithrombin III-complex (TATIII) at 8 h as a si gn of procoagulatory activity is accompanied by the inhibition of fibr inolysis, reflected by high concentrations of plasminogen-activator-in hibitor-1 (PAI-1) at 8 h and at 24 h. Peak levels of D-Dimer at 8 h ar e followed by a steady decline toward baseline. Positive post mortem i mmunostaining for fibrin in lung sections confirms the biochemical fin dings. Surfactant impairment is demonstrated by a significant decrease in the stability index and the hysteresis area lasting up to 48 h. We conclude that we have created a protocol in the baboon which describe s the intraalveolar coagulatory disorders found in acute lung injury t ogether with the factors exerting inhibitory effects on pulmonary surf actant. We further conclude that this model provides a tool for ongoin g investigations in this field of research.