Abstract
Background
: The immunomodulatory effects of hypertonic saline (HTS) provide potential strategies to attenuate inappropriate inflammatory reactions. This study tested the hypothesis that administration of intratracheal aerosolized HTS modulates the development of lung injury in pancreatitis.
Methods
: Pancreatitis was induced in 24 male Sprague-Dawley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). At 24 and 48 h, intratracheal aerosolized HTS (7.5% NaCl, 0.5 mL) was administered to 8 rats, while a further 8 received 0.5 mL of aerosolized normal saline (NS). At 72 hours, pulmonary neutrophil infiltration (myeloperoxidase activity) and endothelial permeability (bronchoalveolar lavage and wet:dry weight ratios) were assessed. In addition, histological assessment of representative lung tissue was performed by a blinded assessor. In a separate experiment, polymorphonucleocytes (PMN) were isolated from human donors, and exposed to increments of HTS. Neutrophil transmigration across an endothelial cell layer, VEGF release, and apoptosis at 1, 6, 12, 18, and 24 h were assessed.
Results
: Histopathological lung injury scores were significantly reduced in the HTS group (4.78 ± 1.43 vs. 8.64 ± 0.86); p < 0.001). Pulmonary neutrophil sequestration (1.40 ± 0.2) and increased endothelial permeability (6.77 ± 1.14) were evident in the animals resuscitated with normal saline when compared with HTS (0.70 ± 0.1 and 3.57 ± 1.32), respectively; p < 0.04). HTS significantly reduced PMN transmigration (by 97.1, p = 0.002, and induced PMN apoptosis (p < 0.03). HTS did not impact significantly upon neutrophil VEGF release (p > 0.05).
Conclusions
: Intratracheal aerosolized HTS attenuates the neutrophil-mediated pulmonary insult subsequent to pancreatitis. This may represent a novel therapeutic strategy.
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