Ventilation with negative airway pressure induces a cytokine response in isolated mouse lung.

Abstract

We tested the hypothesis that, under relatively low tidal volume (VT) mechanical ventilation, continuing lung decruitment induced by negative end-expiratory pressure (NEEP) would increase the lung cytokine response, potentially contributing to lung injury. Mouse lungs were excised and randomly assigned to one of 3 different ventilatory strategies: 1) the zero end-expiratory pressure group served as a control, 2) the NEEP7 group received a NEEP of -7.5 cm H(2)O, and 3) the NEEP15 group received a NEEP of -15 cm H(2)O. In all 3 groups, a VT of 7 mL/kg was used. After 2 h of ventilation, lung lavage fluid was collected for measurements of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and lactate dehydrogenase. Increases in plateau pressure before and after mechanical ventilation were significantly greater in the NEEP15 group compared with the zero end-expiratory pressure group or NEEP7 group. Lung compliance was decreased in the NEEP15 compared with the other two groups. Concentrations of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and lactate dehydrogenase in lung lavage were larger in the NEEP15 group than in the other groups. Atelectatic lung during repeated collapse and reopening of lung units accentuates the lung cytokine response that may contribute to lung injury even during relatively low VT mechanical ventilation. Repeated closing and reopening of lung units induced by negative end-expiratory pressure resulted in lung inflammation and cell injury even under mechanical ventilation using a normal tidal volume. This finding may have clinical relevance in certain patients who are prone to atelectasis during mechanical ventilation.