Hyperoxia Exacerbates Microvascular Lung Injury Following Acid Aspiration (original) (raw)

Objectives: To examine the effects ofan increase in ambient oxygen (<32) concentrations on the extent of inflammatory pulmonary damage following acid aspiration. Design: Prospective, controlled laboratory study. Settings: University-affiliated animal research facility. Subjects: Male, Long Evans rats weighing 250 to 300 g. Intervention: Rats were injured by instillation of 1.2 mL/kg normal saline solution/HCl, pH=1.25 (acid), into the lungs via a tracheotomy. Animals were allowed to awaken and were exposed to 21%, 50%, or 98% 02 for 0 to 5 h (n/group^lO). In a separate set of experiments, injured rats exposed to 98% 02 were treated with different doses of deferoxamine, just prior to injury. Uninjured rats and rats injured with normal saline solution, pH=5.3, were used as the control group. Measurements: Injury was determined by assessing lung function (lung compliance and arterial blood gases) and alveolar-capillary wall integrity (wet/dry weight, lung albumin permeability index [PI], and intrapulmonary hemorrhage [HI]). Results: Intrapulmonary instillation of acid increased PI, HI, and decreased static lung compliance compared to uninjured control animals. Increased ambient oxygen following acid aspiration de¬ creased lung compliance, 1.06±0.03 mL/kg/cm H20, in oxygen-exposed lungs when compared to the lungs exposed to air, 1.26 ±0.04, following a low pH aspirate (p<0.05). An increase in protein leakage into the lung tissue was noted in oxygen-exposed animals, PI=1.33 ±0.10, vs air-exposed rats, 0.89±0.07 (p<0.05). The hyperoxia-induced increase in lung injury was prevented by 30 mg/kg or higher deferoxamine treatment, 0.78±0.05 (p<0.05). Exposure of animals to 98% 02 for 2 h was sufficient to produce the same increase in microvascular protein leakage as 5-h exposure to 02 following low pH aspirate. Conclusion: Hyperoxia increases acid aspiration-induced inflammatory microvascular lung injury. This appears to be mediated by production of reactive species of 02.