Different ventilation strategies affect lung function but do not increase tumor necrosis factor-α and prostacyclin production in lavaged rat lungs in vivo

Background: Using an in vitro animal model of surfactant deficiency, the authors compared the effect of different ventilation strategies on oxygenation and inflammatory mediator release from the lung parenchyma. Methods: In adult rats that were mechanically ventilated with 100% oxygen, acute lung injury was induced by repeated lung lavage to obtain an arterial oxygen partial pressure < 85 mmHg (peak pressure/positive end-expiratory pressure [PEEP] = 26/6 cm H2O). Animals were then randomly assigned to receive either erogenous surfactant therapy, partial liquid ventilation, ventilation with high PEEP (16 cm H2O), ventilation with low PEEP (8 cm H2O), or ventilation with an increase in peak inspiratory pressure (to 32 cm H2O; PEEP = 6 cm H2O). Two groups of healthy nonlavaged rats were ventilated at a peak pressure/PEEP of 32/6 and 32/0 cm H2O, respectively. Blood gases were measured. Prostacyclin (PGI(2)) and tumor necrosis factor-alpha (TNF-alpha) concentrations in serum and bronchoalveolar lavage fluid (BALF) as well as protein concentration in BALF were determined after 30 and 240 min and compared with mechanically ventilated and spontaneously breathing controls. Results: Surfactant, partial liquid ventilation, and high PEEP improved oxygenation and reduced BALF protein levels. Ventilation with high PEEP at high mean airway pressure levels increased BALF PGI(2) levels, whereas there was no difference in BALF TNF-alpha levels between groups. Serum PGI(2) and TNF-alpha levels did not increase as a result of mechanical ventilation when compared with those of spontaneously breathing controls. Conclusions: Although alveolar protein concentration and oxygenation markedly differed with different ventilation strategies in this model of acute lung injury, there were no indications of ventilation-induced systemic PGI(2) and TNF-alpha release, nor of pulmonary TNF-alpha release. Mechanical ventilation at high mean airway pressure levels increased PGI(2) levels in the bronchoalveolar lavage-accessible space.