Beta-adrenergic modulation of lung fluid balance in acute P aeruginosa pneumonia in rats

Abstract

ABSTRACTObjective: we investigated the effects of terbutaline, a ß2-adrenergic agonist, on lung permeability and alveolar fluid clearance (AFC) in acute lung injury (ALI). Methods: the study was conducted in vivo on a rat model of P aeruginosa (Pa)-induced ALI. Rats were randomly divided into five groups: the control group (saline group), Pa and saline group, Pa and terbutaline treated group receiving intratracheal instillation of terbutaline at 10−4 M, Pa and terbutaline plus propranolol treated group (terbutaline+propranolol group) and Pa and propranolol treated group (propranolol group). Hemodynamics, airway pressures, arterial blood gases, extravascular lung water, lung permeability to protein evaluated by the extravascular accumulation of 125I-albumin (EPE), bacterial counts, and alveolar fluid clearance (AFC) were measured. Results: 4.5 hours after bacterial instillation, the lung wet-to-dry ratio and the EPE were significantly decreased in the terbutaline group compared to saline control group (respectively 4.31 ± 0.51 g/g versus 5.99 ± 0.5 g/g 4.18 ± 0.25 g/g and 148 ± 68 μL versus 349 ± 97 μL respectively p < 0.01). Treatment with terbutaline in the Pa-instilled group significantly increased basal AFC compared with the saline and Pa group, (respectively 22.3 ± 1.3% versus 12.5 ± 4.7%, p < 0.001). Intratracheal instillation of propranolol (10−4 M) inhibited the effects of terbutaline on lung fluid balance. Conclusion: Exogenous instillation of beta2-adrenergic have a beneficial effect on lung fluid balance following Pa pneumonia in rats, by reducing pulmonary endothelial permeability and increasing alveolar fluid clearance. These data suggest that exogenous beta-adrenergic therapy can protect against alveolar edema formation in acute P aeruginosa pneumonia.