Ventilation-induced lung injury in rats is associated with organ injury and systemic inflammation that is attenuated by dexamethasone.
OBJECTIVE
To determine whether mechanical ventilation using high tidal volume is associated with nonpulmonary organ dysfunction that can be attenuated by dexamethasone.


METHODS
Prospective randomized animal intervention study.


METHODS
Animal care facility in a university hospital.


METHODS
Sedated and tracheostomized male Sprague-Dawley rats.


METHODS
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.


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.
Servicio de Cuidados Intensivos, Hospital Universitario de Getafe, Madrid, Spain.
Nicolás
N
Nin
Oscar
O
Peñuelas
Marta
M
de Paula
José A
JA
Lorente
Pilar
P
Fernández-Segoviano
Andrés
A
Esteban
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000517:prevention & control*; D008171:Lung Diseases / Q000150:complications* / Q000209:etiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone