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Published ahead of print on October 2, 2003, doi:10.1164/rccm.200304-544OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 1, January 2004, 57-63

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Submitted on April 24, 2003
Accepted on September 22, 2003

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

Jay M Steinberg1*, Henry J Schiller2, Jeffrey M Halter1, Louis A Gatto3, Hsi-Ming Lee4, Lucio A Pavone1, and Gary F Nieman1

1 Surgery, State University of New York Upstate Medical University, Syracuse, NY, USA, 2 Surgery, Mayo Medical School, Rochester, MN, USA, 3 Biology, State University of New York Cortland, Cortland, NY, USA, 4 Oral Biology and Pathology, State University of New York Stonybrook, Stonybrook, NY, USA

* To whom correspondence should be addressed. 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 which results in a secondary neutrophil-mediated proteolytic injury. Pigs were mechanically ventilated (tidal volume 10cc/kg, positive end-expiratory pressure (PEEP) 3cmH20), randomized to into 3 groups and followed for 4 hours: Control (n=3) surgery only; Tween (n=4) subjected to intratracheal Tween (surfactant deactivator causing alveolar instability); Tween+PEEP (n=4) subjected to Tween with increased PEEP (15cmH20) 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. To our knowledge, this is the first study to directly confirm that unstable alveoli are subjected to ventilator-induced lung injury while stable alveoli are not.
Key words: VILI, cytokine, in vivo microscopy, alveolar mechanics




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