Augmented lung injury due to interaction between hyperoxia and mechanical ventilation*


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Abstract

Objective:Mechanical overdistension and hyperoxia can independently cause lung injury, yet little is known about their combined effects. We hypothesized that hyperoxia exacerbates lung injury caused by large tidal volume ventilation.Design:Experimental study.Setting:University laboratory.Subjects:Anesthetized, paralyzed rabbits.Interventions:In experiment 1, 12 rabbits were ventilated with 25 mL/kg tidal volumes at positive end-expiratory pressure of 0 cm H2O for 4 hrs with either hyperoxia (HO; Fio2 = 0.5) or normoxia (NO; Fio2 = 0.21). In experiment 2, a separate group of animals were randomized to one of four groups to assess the interaction of tidal volume and inspired oxygen concentration on potential mediators of injury after 2 hrs of ventilation, before significant injury occurs: a) NO+normal tidal volume (NV; Vt = 10 mL/kg); b) HO+NV; c) NO+high tidal volume (HV; Vt = 25 mL/kg); d) HO+HV (n = 3 per group).Measurements and Main Results:In the first study, HO compared with the NO group had significantly reduced Pao2/Fio2 ratio (320 ± 110 vs. 498 ± 98, p = .014) and increased lung injury scores at 4 hrs. Hyperoxia also significantly increased polymorphonuclear leukocytes, growth-related oncogene-α (2073 ± 535 vs. 463 ± 236 pg/mL, p = .02), and monocyte chemotactic protein-1 (7517 ± 1612 vs. 2983 ± 1289 pg/mL, p = .05) concentrations in bronchoalveolar lavage fluid. The second study showed increased alveolar-capillary permeability to a 70-kD fluorescent-labeled dextran only in response to the combination of both HO and HV. Chemokines and bronchoalveolar lavage fluid neutrophils were elevated in both HV groups; however, hyperoxia did not further increase chemokine or neutrophil counts over normoxia. No difference in lipid peroxidation was seen between groups.Conclusions:Moderate hyperoxia exacerbates lung injury in a large tidal volume model of ventilator-induced lung injury. The mechanism by which this occurs is not mediated by increased production of CXC chemokines or lipid peroxidation.

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