Interactions of lung stretch, hyperoxia, and MIP-2 production in ventilator-induced lung injury.
The use of positive pressure mechanical ventilation can cause ventilator-induced lung injury (VILI). We hypothesized that hyperoxia in combination with large tidal volumes (VT) would accentuate noncardiogenic edema and neutrophil infiltration in VILI and be dependent on stretch-induced macrophage inflammatory protein-2 (MIP-2) production. In rats ventilated with VT 20 ml/kg, there was pulmonary edema formation that was significantly increased by hyperoxia. Total lung neutrophil infiltration and MIP-2 in bronchoalveolar lavage (BAL) fluid were significantly elevated, in animals exposed to high VT both on room air (RA) and with hyperoxia. Hyperoxia markedly augmented the migration of neutrophils into the alveoli. Anti-MIP-2 antibody blocked migration of neutrophils into the alveoli in RA by 51% and with hyperoxia by 65%. We concluded that neutrophil migration into the alveoli was dependent on stretch-induced MIP-2 production. Hyperoxia significantly increased edema formation and neutrophil migration into the alveoli with VT 20 ml/kg, although BAL MIP-2 levels were nearly identical to VT 20 ml/kg with RA, suggesting that other mechanisms may be involved in hyperoxia-augmented neutrophil alveolar content in VILI.
Pulmonary/Critical Care Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. dquinn1@partners.org
Deborah A
DA
Quinn
Ramzi K
RK
Moufarrej
Alexey
A
Volokhov
Charles A
CA
Hales
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D054426:Chemokine CXCL2; D015633:Extravascular Lung Water / Q000378:metabolism; D018496:Hyperoxia / Q000276:immunology* / Q000378:metabolism; D015846:Monokines / Q000096:biosynthesis* / Q000276:immunology; D009504:Neutrophils / Q000166:cytology; D011650:Pulmonary Alveoli / Q000276:immunology / Q000293:injuries* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*
D000906:Antibodies; D054426:Chemokine CXCL2; D015846:Monokines