Pulmonary Pharmacology & Therapeutics

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Background: Lung transplantation is a treatment method for end stage lung disease, but the availability of donor lungs remains a major constraint. Brain death (BD) induces hemodynamic instability with microcirculatory hypoperfusion and increased inflammation, leading to pulmonary dysfunction. Hypertonic saline solution (HSS) is a volume expander possessing immunomodulatory effects. This study evaluated the influence of HSS on pulmonary dysfunction and inflammation in a rat model of BD. Methods: BD was induced by inflation of an intracranial balloon catheter. Rats were divided into: (1) Sham, without BD; (2) NS, NaCl treatment (0.9%, 4 mL/kg, i.v.) immediately after BD; (3) HSS1, HSS treatment (NaCl 7.5%, 4 mL/kg, i.v.) immediately after BD; and (4) HSS60, HSS treatment 60 min post BD. All groups were analyzed after 360 minutes. Results: Animals subjected to BD exhibited increased exhaled O2 and decreased CO2.The number of leukocytes in the lungs was significantly increased in the NS group (p=0.002) and the HSS treatment was able to reduce it (HSS1, p=0.018 and HSS60= 0.030). In parallel, HSS-treated rats showed reduced levels of ICAM-1 expression, which was increased in the NS respective to Sham group. Lung edema was found increased in the NS group animals compared to Sham and no effect of the HSS treatment was observed. There were no differences among the groups in terms of TNF-α, VEGF, and CINC-1 lung concentrations. Conclusions: HSS is capable of reducing inflammatory cell infiltration into the lung after BD induction, which is associated with the reduction of ICAM-1 expression in organ vessels.

EFS-induced contractions in human bronchi of different sizes (Figure S1). Effect of tiotropium on EFS-induced contractions in human bronchi of different sizes (Figure S2).