Bacteremia-induced suppression of alveolar surfactant production.
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 vivo. A technique for estimation of pulmonary surfactant phospholipid synthesis measuring incorporation of a stable isotope precursor [( 2-13C]acetate) into dipalmitoylphosphatidylcholine (DPPC) in alveolar lavage fluid was developed. Male 350 g Sprague-Dawley rats had placement of central venous catheters. After overnight recovery, sublethal bacteremia (Escherichia coli, 1 x 10(8) 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 [2-13C]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 greater than 0.05] and bacteremic animals had a 56.9% diminution of [2-13C]acetate incorporation [1.215 +/- 0.145 APE (%) sham versus 0.524 +/- 0.56 APE (%) experimental, P less than 0.05]. Bacteremia-induced dysfunction of alveolar type II epithelial cells manifested as diminished alveolar surfactant phospholipid production may be a contributing factor to sepsis-induced respiratory failure.
Oldham
K T
KT
Department of Surgery, Upjohn Center for Clinical Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0245.
Guice
K S
KS
Stetson
P S
PS
Wolfe
R R
RR
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000096:biosynthesis; D000085:Acetates / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000473:pathology; D004927:Escherichia coli Infections / Q000378:metabolism* / Q000473:pathology; D008401:Gas Chromatography-Mass Spectrometry; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008297:Male; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D018805:Sepsis / Q000378:metabolism* / Q000473:pathology
D000085:Acetates; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine