Bacteremia-Induced Suppression of Alveolar Surfactant Production1*2

Sepsis is characterized by Adult Respiratory Distress Syndrome (ARDS)-like pulmonary dysfunction largely attributed to alveolar capillary endothelial cell injury which causes increased microvascular permeability and interstitial edema formation. In addition, quantitative and qualitative abnormalities of the pulmonary surfactant system may be important features of some clinical and experimental lung injuries. This study was designed to investigate the relationship of bacteremia and endotoxemia to pulmonary surfactant production in viva. A technique for estimation of pulmonary surfactant phospholipid synthesis measuring incorporation of a stable isotope precursor ([2lSC]acetate) into dipalmitoylphosphatidylcholine (DPPC) in alveolar lavage fluid waideveloped. Male 350 g Sprague-Dawley rats had placement of central venous catheters. After overnight recovery, sublethal bacteremia (Escherichia coli, 1 X lOa organisms, iv) and sublethal endotoxemia (Difco; 10 mg/kg, iv) were induced. Both were associated with lung microvascular permeability increases consistent with capillary endothelial injury. Eight-hour infusions of [2-lSC]acetate were given. After sacrifice, bronchoalveolar washings and lung tissue were obtained and [2-13C] incorporation into lavage and lung DPPC was measured by gas chromatography mass spectroscopy. Endotoxin-treated animals had a 21.5% reduction in label incorporation into DPPC [1.215 ? 0.145 APE (%) sham versus 0.954 ? 0.144 APE (%) experimental, P > 0.051 and bacteremic animals had a 56.9% diminution of [2-“Clacetate incorporation [1.215 + 0.145 APE (Yo) sham versus 0.524 + 0.56 APE (%) experimental, P < 0.051. Bacteremiainduced dysfunction of alveolar type II epithelial cells manifested as diminished alveolar surfactant phospholipid production may be a contributing factor to sepsisinduced respiratory failure. o 1989 Academic PEWS, h.