Reduction in alveolar macrophages attenuates acute ventilator induced lung injury in rats

Objective: Alveolar macrophages are the sentinel cell for activation of the inflammatory cascade when the lung is exposed to noxious stimuli. We investigated the role of macrophages in mechanical lung injury by comparing the effect of high- volume mechanical ventilation with or without prior depletion of macrophages. Design and setting: Randomized sham- controlled animal study in anesthetized rats. Methods: Lung injury was induced by 15 min of mechanical ventilation (intermittent positive pressure ventilation) using high peak pressures and zero end- expiratory pressure. The mean tidal volume was 40 +/- 0.7ml/ kg. One group of animals was killed immediately after this period of volutrauma (HV), while in a second group normoventilation was continued for 2 h at a tidal volume less than 10 ml/ kg (HV-LV). One- half of the animals were depleted of alveolar macrophages by pretreatment with intratracheal liposomal clodronate (CL2MDP). Measurements: Arterial blood gas, blood pressure. After kill: lung static pressure volume curves, bronchoalveolar fluid concentration for protein, macrophage inflammatory protein 2, tumor necrosis factor a, and wet/ dry lung weight ratio (W/D). Results: During HV and HV+ LV oxygenation, lung compliance, and alveolar stability were better preserved in animals pretreated with CL2MDP. In both groups W/ D ratio was significantly greater in ventilated than in nonventilated animals (4.5 +/- 0.6), but the increase in W/ D was significantly less in CL2MDP treated HV and HV- LV groups (6.1 +/- 0.4, 6.6 +/- 0.6) than in the similarly ventilated nontreated groups (8.7 +/- 0.2 and 9.2 +/- 0.5). Conclusions: Alveolar macrophages participate in the early phase of ventilator- induced lung injury.