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Am. J. Respir. Crit. Care Med., Volume 165, Number 2, January 2002, 242-249

Low Tidal Volume Reduces Epithelial and Endothelial Injury in Acid-injured Rat Lungs

JAMES A. FRANK, JORGE A. GUTIERREZ, KIRK D. JONES, LENNELL ALLEN, LELAND DOBBS, and MICHAEL A. MATTHAY

Cardiovascular Research Institute and the Departments of Medicine, Anesthesia, Pediatrics, and Pathology, University of California, San Francisco, San Francisco, California

Using a rat model of acid-induced lung injury, we tested the hypothesis that tidal volume reduction at the same level of PEEP (10 cm H2O) would diminish the degree of pulmonary edema by attenuating injury to the alveolar epithelial and endothelial barriers. Tidal volume reduction from 12 to 6 to 3 ml/kg significantly reduced the rate of lung water accumulation from 690 µl/h to 310 µl/h to 210 µl/h. Ventilation with either 6 or 3 ml/kg reduced endothelial injury equally as measured by plasma vWf:Ag and permeability to albumin. Plasma RTI40, a marker of type I epithelial cell injury, decreased 46% when tidal volume was reduced from 12 to 6 ml/kg and decreased an additional 33% with 3 ml/kg (p < 0.05). The rate of alveolar epithelial fluid clearance was significantly faster in the 3-ml/kg group (24 ± 7%/h) compared with 6 ml/kg (15 ± 11%/h) and 12 ml/kg (3 ± 6%/h). We conclude that low tidal volume ventilation protects both the alveolar epithelium and the endothelium in this model of acute lung injury. The additional decrease in pulmonary edema with a tidal volume of 3 ml/kg is partly accounted for by greater protection of the alveolar epithelium.




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