Natural surfactant and hyperoxic lung injury in primates. I. Physiology and biochemistry.
Surfactant dysfunction contributes to the pathophysiology of adult respiratory distress syndrome (ARDS), and we hypothesized that surfactant treatment would improve experimental ARDS produced by continuous exposure to hyperoxia. Twelve healthy male baboons (10-15 kg) were anesthetized, paralyzed, and mechanically ventilated with 2.5 cmH2O positive end-expiratory pressure (PEEP) for 96 h. Baboons were divided into three groups: 1) the O2 group (n = 5) received 100% O2, 2) the surfactant group (n = 5) received 100% O2 and aerosolized porcine surfactant, and 3) a control group (n = 2) was ventilated at fractional concentration of inspired O2 of 0.21 for 96 h to control for effects of anesthesia and mechanical ventilation. Hemodynamic parameters were obtained every 12 h, and ventilation-perfusion (VA/Q) distribution was measured daily by multiple inert gas elimination technique. PEEP was increased once or twice daily to 10 cmH2O for 30 min to study its effects on measurements of VA/Q. At the end of experiments, lungs were obtained for biochemical analysis. Prolonged hyperoxia resulted in progressive worsening in VA/Q, hemodynamic deterioration, severe lung edema, and altered surfactant metabolism. Surfactant administration increased disaturated phosphatidylcholine in lavage fluid but did not improve lung edema or gas exchange. In the surfactant group, however, the addition of 10 cmH2O PEEP resulted in a greater degree of shunt reduction than did 2.5 cmH2O PEEP (47 vs. 31% in the O2 group, P < 0.05). We conclude that aerosolized porcine surfactant did not prevent pulmonary O2 injury in baboons, but it potentiated the shunt-reducing effect of PEEP.
Huang
Y C
YC
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Caminiti
S P
SP
Fawcett
T A
TA
Moon
R E
RE
Fracica
P J
PJ
Miller
F J
FJ
Young
S L
SL
Piantadosi
C A
CA
D000336:Aerosols; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D006439:Hemodynamics / Q000187:drug effects; D008033:Limulus Test; D008297:Male; D010100:Oxygen / Q000633:toxicity*; D010215:Papio; D011175:Positive-Pressure Respiration; D011510:Proteolipids / Q000032:analysis / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000517:prevention & control; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D012129:Respiratory Function Tests; D013552:Swine; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects / Q000502:physiology
D000336:Aerosols; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D010100:Oxygen