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Depts of 1 Medicine, 2 Physiology and the 3 Lawson Research Institute, University of Western Ontario and 4 Dept of Pathology, St Joseph’s Health Centre, London, Canada. 5 Depts of Medicine and Surgery and the Samuel Lunenfeld Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada
CORRESPONDENCE: R. Veldhuizen, Lawson Research Institute, Room G454, 268 Grosvenor Street, London, Ontario, Canada, N6A 4V2. Fax: 1 5196466110
Keywords: ARDS, lung injury, mechanical ventilation, surfactant
Received: November 19, 1999
Accepted May 17, 2000
This
work was supported by a grant from the Ontario Thoracic Society.
Mechanical ventilation of the lung is an essential but potentially harmful
therapeutic intervention for patients with acute respiratory distress syndrome.
The objective of the current study was to establish and characterize an isolated
mouse lung model to study the harmful effects of mechanical ventilation.
Lungs were isolated from BalbC mice and randomized to either a nonventilated
group, a conventionally ventilated group (tidal volume 7 mL·kg–1, 4 cm positive end-expiratory pressure (PEEP))
or an injuriously ventilated group (20 mL·kg–1,
0 cm PEEP). Lungs were subsequently analysed for lung compliance, morphology,
surfactant composition and inflammatory cytokines.
Injurious ventilation resulted in significant lung dysfunction, which was
associated with a significant increase in pulmonary surfactant, and surfactant
small aggregates compared to the other two groups. Injurious ventilation also
led to a significantly increased concentration of interleukin-6 and tumour
necrosis factor-
It was concluded that the injurious effects of mechanical ventilation can
effectively be studied in isolated mouse lung, which offers the potential
of studying genetically altered animals. It was also concluded that in this
model, the lung injury is, in part, mediated by the surfactant system and
the release of inflammatory mediators.
in the lavage.
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