Effects of cyclic opening and closing at low- and high-volume ventilation on bronchoalveolar lavage cytokines*

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Abstract
To examine the mechanisms of ventilator-induced lung injury at low and high lung volumes. Prospective, randomized, laboratory study. University research laboratory. Eighty-eight adult male Sprague-Dawley rats. Mechanical ventilation using low and high lung volumes. An ex vivo rat lung model was used. In study I (ventilation at low lung volumes), rat lungs (n = 40) were randomly assigned to various modes of ventilation: a) opening and closing with positive end-expiratory pressure (PEEP; control): tidal volume 7 mL/kg and PEEP 5 cm H2O; b) opening and closing from zero end-expiratory pressure (ZEEP): tidal volume 7 mL/kg and PEEP 0; or c) atelectasis. Peak inspiratory pressure was monitored at the beginning and end of 3 hrs of ventilation. At the end of 3 hrs of ventilation, the lungs were lavaged, and the concentrations of tumor necrosis factor-α, macrophage inflammatory protein-2, and interleukin-6 cytokines were measured in the lavage. In study II (ventilation at high volumes), rat lungs (n = 45) were randomly assigned to a) cyclic lung stretch: pressure-controlled ventilation, peak inspiratory pressure 50 cm H2O, and PEEP 8 cm H2O; b) continuous positive airway pressure at 50 cm H2O (CPAP50); or c) CPAP at the mean airway pressure of the cyclic stretch group (CPAP 31 cm H2O). Bronchoalveolar lavage cytokine concentrations (tumor necrosis factor-α, macrophage inflammatory protein-2, and interleukin-6) were measured at the end of 3 hrs of ventilation. In the low volume study, there was no difference in bronchoalveolar lavage cytokine concentrations between the PEEP group and the atelectatic group. All cytokines were significantly higher in the ZEEP group compared with the atelectasis group. Macrophage inflammatory protein-2 was significantly higher in the ZEEP group compared with the PEEP group. Lung compliance, as reflected by change in peak inspiratory pressure, was also significantly worse in the ZEEP compared with the PEEP group. In the high-volume study, tumor necrosis factor-α and interleukin-6 were significantly higher in the cyclic stretch group compared with the CPAP 31 group. There was no significant difference between the cytokine concentrations in the cyclic stretch group compared with the CPAP 50 group. We conclude that at low lung volumes, cyclic opening and closing from ZEEP leads to greater increases in bronchoalveolar lavage cytokines than atelectasis. With high-volume ventilation, over time, the degree of overdistension is more associated with increases in bronchoalveolar lavage cytokines than cyclic opening and closing alone.