title: Alterations to surfactant precede physiological deterioration during high tidal volume ventilation.
abstract: Lung injury due to mechanical ventilation is associated with an impairment of endogenous surfactant. It is unknown whether this impairment is a consequence of or an active contributor to the development and progression of lung injury. To investigate this issue, the present study addressed three questions: Do alterations to surfactant precede physiological lung dysfunction during mechanical ventilation? Which components are responsible for surfactant's biophysical dysfunction? Does exogenous surfactant supplementation offer a physiological benefit in ventilation-induced lung injury? Adult rats were exposed to either a low-stretch [tidal volume (Vt) = 8 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O, respiratory rate (RR) = 54-56 breaths/min (bpm), fractional inspired oxygen (Fi(O2)) = 1.0] or high-stretch (Vt = 30 ml/kg, PEEP = 0 cmH2O, RR = 14-16 bpm, Fi(O2) = 1.0) ventilation strategy and monitored for either 1 or 2 h. Subsequently, animals were lavaged and the composition and function of surfactant was analyzed. Separate groups of animals received exogenous surfactant after 1 h of high-stretch ventilation and were monitored for an additional 2 h. High stretch induced a significant decrease in blood oxygenation after 2 h of ventilation. Alterations in surfactant pool sizes and activity were observed at 1 h of high-stretch ventilation and progressed over time. The functional impairment of surfactant appeared to be caused by alterations to the hydrophobic components of surfactant. Exogenous surfactant treatment after a period of high-stretch ventilation mitigated subsequent physiological lung dysfunction. Together, these results suggest that alterations of surfactant are a consequence of the ventilation strategy that impair the biophysical activity of this material and thereby contribute directly to lung dysfunction over time.
authors.affiliation: Lawson Health Research Institute F4-117, 268 Grosvenor St., London, ON, Canada, N6A 4V2.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Maruscak
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Vockeroth
authors.forename: Brandon
authors.initials: B
authors.lastname: Girardi
authors.forename: Tanya
authors.initials: T
authors.lastname: Sheikh
authors.forename: Fred
authors.initials: F
authors.lastname: Possmayer
authors.forename: James F
authors.initials: JF
authors.lastname: Lewis
authors.forename: Ruud A W
authors.initials: RA
authors.lastname: Veldhuizen
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000097:blood; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism*; D037701:Pulmonary Surfactant-Associated Protein B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013990:Tidal Volume; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D010100:Oxygen