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A7524 - Progressive Increase in Tidal Volume Protected Against Lung Injury in Experimental Mild Acute Respiratory Distress Syndrome
Author Block: N. Felix1, C. D. Samary1, F. F. Cruz1, N. d. Rocha2, M. Fernandes1, J. Machado1, R. Bose-Madureira1, M. Gama de Abreu3, P. Pelosi4, P. L. Silva1, J. J. Marini5, P. R. Rocco1; 1Carlos Chagas Filho Institute of Biophysics, Laboratory of Pulmonary Investigation, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 2Physiology, Universidade Federal Fluminense, Niteroi, Brazil, 3Department of Anesthesiology and Intensive Care Therapy, Dresden University Technology, Dresden, Germany, 4Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genova, Italy, 5Department of Medicine, University of Minnesota, Minnesota, MN, United States.
RATIONALE: In acute respiratory distress syndrome (ARDS), injury to the lungs is heterogeneous, with areas of alveolar collapse and overdistension, which may lead to ventilator-induced lung injury (VILI) depending on the ventilation strategy adopted. As a result, inhomogeneous distribution of air within the lungs is observed, which, combined with high tidal volumes (VT), may yield further lung damage. However, this deleterious effect may be associated with a sudden increase in VT (and dynamic strain). We hypothesized that damage caused by high tidal volumes would be attenuated if VT were raised slowly enough to allow alveoli to open and adapt to the higher VT target (VTH). METHODS: Thirty-two rats (330-500g) received E. coli lipopolysaccharide intratracheally (200 µg). After 24h, animals were ventilated for 5 min with VT=6ml/kg, respiratory rate adjusted to a minute ventilation of 160ml/min, positive end-expiratory pressure=3cmH2O, and fraction of inspired oxygen=0.4. Data were collected at baseline and rats were randomly assigned to four groups: (A) mechanical ventilation with protective strategy (VT=6ml/kg) for 2 hours; (B) VT=6ml/kg during hour 1 followed by constant VT=22ml/kg in hour 2; (C) VT=6ml/kg during the first 30 minutes followed by a slow VT increase up to 22ml/kg for 30 minutes, then constant VT=22ml/kg during hour 2; and (D) a slow VT increase from 6ml/kg to 22ml/kg during hour 1 followed by constant VT=22ml/kg during hour 2. Echocardiography was performed hourly. After 2h, lungs were removed for histology and molecular biology analyses. Expression of interleukin (IL)-6, amphiregulin, metalloproteinase (MMP)-9, syndecan, and epithelial cell injury (club cell secretory protein [CC]-16) was measured. RESULTS: The VTH led to increased plateau pressure, driving pressure, energy load, and mechanical power. Cardiac output was reduced by VTH in B (abrupt application of VTH) compared to other groups. IL-6 mRNA expression was higher in B and D than non-ventilated (NV) animals and A, and higher in B and D than C. Amphiregulin expression was increased in B (3.6±2.6) and D (2.6±0.5) compared to NV (1.0±0.3), A (2.0±1.2), and C (1.7±1.6). MMP-9 expression was increased only in B (3.6±2.6) compared to NV (1.0±0.3) and A (2.0±1.2). Syndecan expression was higher in B (1.9±1.4) compared to groups A (0.7±0.6), C (0.8±0.5), and D (0.5±0.3). CC-16 expression was higher in B (2.4±0.9) and D (2.1±1.4) compared to C (0.8±0.5). CONCLUSION: In experimental mild ARDS, a progressive increase of VT to VTH might minimize VILI. Gradual accommodation may reduce lung inhomogeneity and dynamic strain.