Ventilation-induced lung injury in rats is associated with organ injury and systemic inflammation that is attenuated by dexamethasone

Crit Care Med. 2006 Apr;34(4):1093-8. doi: 10.1097/01.CCM.0000205663.92384.E7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Dexamethasone / therapeutic use*
  • Humans
  • Inflammation / etiology*
  • Inflammation / prevention & control*
  • Lung Diseases / complications*
  • Lung Diseases / etiology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Respiration, Artificial / adverse effects*

Substances

  • Anti-Inflammatory Agents
  • Dexamethasone