Alterations to surfactant precede physiological deterioration during high tidal volume ventilation.
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.
Maruscak
Adam A
AA
Lawson Health Research Institute F4-117, 268 Grosvenor St., London, ON, Canada, N6A 4V2.
Vockeroth
Daniel W
DW
Girardi
Brandon
B
Sheikh
Tanya
T
Possmayer
Fred
F
Lewis
James F
JF
Veldhuizen
Ruud A W
RA
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
D015850:Interleukin-6; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D010100:Oxygen