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.


METHODS
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+/-0.7 ml/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).


METHODS
Arterial blood gas, blood pressure. After kill: lung static pressure volume curves, bronchoalveolar fluid concentration for protein, macrophage inflammatory protein 2, tumor necrosis factor alpha, 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.
Eyal
Fabien G
FG
Department of Pediatrics, Children's and Women's Hospital, University of South Alabama, 1700 Center Street, 36604, Mobile, AL, USA. fgeyal@aol.com.|Department of Pediatrics, University of South Alabama, Mobile, AL, USA. fgeyal@aol.com.
Hamm
Charles R
CR
Department of Pediatrics, University of South Alabama, Mobile, AL, USA.
Parker
James C
JC
Department of Physiology, University of South Alabama, Mobile, AL, USA.
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002245:Carbon Dioxide / Q000097:blood; D004002:Clodronic Acid / Q000494:pharmacology; D004195:Disease Models, Animal; D008168:Lung / Q000473:pathology*; D008170:Lung Compliance; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D009929:Organ Size; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D053717:Pneumonia, Ventilator-Associated / Q000209:etiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013990:Tidal Volume; D012122:Ventilators, Mechanical / Q000009:adverse effects*
D004002:Clodronic Acid; D002245:Carbon Dioxide; D010100:Oxygen