Submitted on December 19, 2007
Accepted on March 9, 2008
Alterations to surfactant precede physiological deterioration during high tidal volume ventilation
Adam A. Maruscak1, Daniel W Vockeroth1, Brandon Girardi1, Tanya A Sheikh2, Fred Possmayer3, James F. Lewis4, and Ruud A.W. Veldhuizen1*
1 Physiology and Pharmacology, The University of Western Ontario, London, Canada; Critical Care Medicine, Lawson Health Research Institute, London, Canada
2 Critical Care Medicine, Lawson Health Research Institute, London, Canada
3 Department of Obstetrics & Gynaecology, University of Western Ontario, London, Canada; Department of Biochemistry, University of Western Ontario, Schulich School of Medicine and Dentistry, London, N6A 4C1, Canada
4 Physiology and Pharmacology, The University of Western Ontario, London, Canada; Division of Respirology, St. Joseph's Health Center, London, Canada; Critical Care Medicine, Lawson Health Research Institute, London, Canada
* To whom correspondence should be addressed. E-mail: rveldhui{at}uwo.ca.
Lung injury due to mechanical ventilation is associated with an impairment of endogenous surfactant. It is unknown if this impairment is a consequence of, or an active contributor to, the development and progression of lung injury. To investigate this issue, the current 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 VILI? Adult rats were exposed to either a low stretch (Vt=8 mL/kg, PEEP=5 cm H2O, RR=54-56 bpm, FiO2 = 1.0) or high stretch (Vt=30 mL/kg, PEEP=0 cm H20, RR=14-16 bpm, FiO2 = 1.0) ventilation strategy, and monitored for either 1 or 2 hours. Subsequently animals were lavaged and the composition and function of surfactant was analyzed. Separate groups of animals received exogenous surfactant after 1 hour of high stretch ventilation and were monitored for an additional 2 hours. High stretch induced a significant decrease in blood oxygenation after 2 hours of ventilation. Alterations in surfactant pool sizes and activity were observed at 1 hr 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.
