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This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/L974    most recent 00528.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Maruscak, A. A. Articles by Veldhuizen, R. A. W. PubMed PubMed Citation Articles by Maruscak, A. A. Articles by Veldhuizen, R. A. W.

Alterations to surfactant precede physiological deterioration during high tidal volume ventilation

¹Lawson Health Research Institute, and Departments of ²Medicine, ³Physiology and Pharmacology, ⁴Biochemistry, and ⁵Obstetrics and Gynecology, The University of Western Ontario, London, Ontario, Canada

Submitted 19 December 2007 ; accepted in final form 9 March 2008

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.

mechanical ventilation; biophysical activity; ventilation-induced lung injury