Submitted on October 11, 2007
Accepted on March 3, 2008
Spatial and Temporal Heterogeneity of Ventilator-Associated Lung Injury after Surfactant Depletion
Cynthia M. Otto1, Klaus Markstaller2, Osamu Kajikawa3, Jens Karmrodt2, Rebecca S. Syring4, Birgit Pfeiffer5, Virginia P. Good6, Charles W. Frevert3, and James E. Baumgardner7*
1 Department of Clinical Studies-Philadelphia, University of Pennsylvania, 3900 Delancey St, Philadelphia, Pennsylvania, 19104, United States; Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, 125 S. 31st St, Philadelphia, Pennsylvania, 19104, United States
2 Department of Anesthesiology, Johannes Gutenberg University, Mainz, Germany
3 Deparment of Medicine/Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, Washington, United States
4 Department of Clinical Studies-Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, United States
5 Department of Anesthesiology and Intensive Care Medicine, Otto-von-Guericke University, Magdeburg, Germany
6 Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, 125 S. 31st St, Philadelphia, Pennsylvania, 19104, United States
7 Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania, United States; Oscillogy LLC, Folsom, Pennsylvania, United States
* To whom correspondence should be addressed. E-mail: baumgarj{at}uphs.upenn.edu.
Volutrauma and atelectrauma have been proposed as mechanisms of ventilator-associated lung injury, but few studies have compared their relative importance in mediating lung injury. The objective of our study was to compare the injury produced by stretch (volutrauma) versus cyclical recruitment (atelectrauma) after surfactant depletion. In saline lavaged rabbits, we used high tidal volume, low respiratory rate, and low positive end expiratory pressure to produce stretch injury in nondependent lung regions, and cyclical recruitment in dependent lung regions. Tidal changes in shunt fraction were assessed by measuring arterial PO2 oscillations. After ventilating for times ranging from 0 to 6 hours, lungs were excised, sectioned gravitationally and assessed for regional injury by evaluation of edema formation, chemokine expression, up-regulation of inflammatory enzyme activity, and alveolar neutrophil accumulation. Edema formation, lung tissue interleukin-8 expression and alveolar neutrophil accumulation progressed more rapidly in dependent lung regions, whereas macrophage chemotactic protein-1 expression progressed more rapidly in nondependent lung regions. Temporal and regional heterogeneity of lung injury were substantial. In this surfactant depletion model of acute lung injury, cyclical recruitment produced more injury than stretch.
