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Published ahead of print on October 2, 2003, doi:10.1164/rccm.200304-544OC
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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 57-63, (2004)
© 2004 American Thoracic Society

Alveolar Instability Causes Early Ventilator-induced Lung Injury Independent of Neutrophils

Jay M. Steinberg, Henry J. Schiller, Jeffrey M. Halter, Louis A. Gatto, Hsi-Ming Lee, Lucio A. Pavone and Gary F. Nieman

Department of Surgery, SUNY Upstate Medical University, Syracuse; Department of Biology, SUNY Cortland, Cortland; Department of Oral Biology and Pathology, SUNY Stonybrook, Stonybrook, New York; and Department of Surgery, Mayo Medical School, Rochester, Minnesota

Correspondence and requests for reprints should be addressed to Jay M. Steinberg, D.O., Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, New York, NY 13210. E-mail: steinbja{at}upstate.edu

Intratracheal instillation of Tween causes a heterogeneous surfactant deactivation in the lung, with areas of unstable alveoli directly adjacent to normal stable alveoli. We employed in vivo video microscopy to directly assess alveolar stability in normal and surfactant-deactivated lung and tested our hypothesis that alveolar instability causes a mechanical injury, initiating an inflammatory response that results in a secondary neutrophil-mediated proteolytic injury. Pigs were mechanically ventilated (VT 10 cc/kg, positive end-expiratory pressure [PEEP] 3 cm H20), randomized to into three groups, and followed for 4 hours: Control group (n = 3) surgery only; Tween group (n = 4) subjected to intratracheal Tween (surfactant deactivator causing alveolar instability); and Tween + PEEP group (n = 4) subjected to Tween with increased PEEP (15 cm H20) to stabilize alveoli. The magnitude of alveolar instability was quantified by computer image analysis. Surfactant-deactivated lungs developed significant histopathology only in lung areas with unstable alveoli without an increase in neutrophil-derived proteases. PEEP stabilized alveoli and significantly reduced histologic evidence of lung injury. Thus, in this model, alveolar instability can independently cause ventilator-induced lung injury. To our knowledge, this is the first study to directly confirm that unstable alveoli are subjected to ventilator-induced lung injury whereas stable alveoli are not.

Key Words: ventilator-induced lung injury • cytokine • in vivo microscopy • alveolar mechanics




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