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  • Title: Ventilation-induced lung injury in rats is associated with organ injury and systemic inflammation that is attenuated by dexamethasone.
    Author: Nin N, Peñuelas O, de Paula M, Lorente JA, Fernández-Segoviano P, Esteban A.
    Journal: Crit Care Med; 2006 Apr; 34(4):1093-8. PubMed ID: 16484900.
    Abstract:
    OBJECTIVE: To determine whether mechanical ventilation using high tidal volume is associated with nonpulmonary organ dysfunction that can be attenuated by dexamethasone. DESIGN: Prospective randomized animal intervention study. SETTING: Animal care facility in a university hospital. SUBJECTS: Sedated and tracheostomized male Sprague-Dawley rats. INTERVENTIONS: Three groups of rats were ventilated with different strategies: tidal volume = 9 mL/kg, positive end-expiratory pressure = 8 cm H(2)O, control group (C); tidal volume = 35 mL/kg, positive end-expiratory pressure = 0 cm H(2)O, overventilated group (OV); and tidal volume = 35 mL/kg, positive end-expiratory pressure = 0 cm H(2)O, plus administration of 6 mg/kg dexamethasone intraperitoneally (OV + dexamethasone). All rats were ventilated for 75 mins with respiratory rate = 70 breaths/min, FIO(2) = 0.35, and plateau time = 0. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and peak airway pressure were monitored. We measured arterial blood gases, aspartate aminotransferase, alanine aminotransferase, lactate, nitrates and nitrites, tumor necrosis factor-alpha, and interleukin-6 serum concentration. Lung slices were prepared for blind histologic examination. Heart tissue was analyzed for cyclooxygenase-1 and -2 expression (reverse transcription-polymerase chain reaction). Compared with the C group, the OV group showed hypotension; worsened gas exchange; increased aspartate aminotransferase, lactate, nitrates and nitrites, and interleukin-6 serum concentrations; and hyaline membrane formation in the lungs, as well as increased cyclooxygenase-1 and cyclooxygenase-2 expression in the heart. Dexamethasone prevented the pulmonary and cardiovascular injury and attenuated the increase in aspartate aminotransferase, nitrates and nitrites, interleukin-6, and cyclooxygenase-1 and cyclooxygenase-2 expression. CONCLUSIONS: High tidal volume ventilation induces cardiovascular, pulmonary, and liver injury as well as a systemic proinflammatory response. These changes are attenuated by dexamethasone, suggesting that inflammatory rather than purely hemodynamic mechanisms are involved in the changes induced by high tidal volume ventilation.
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