Benefit of prophylactic bronchodilator with β2 adrenergic agonist in ischemia-reperfusion-induced lung injury

Abstract

Primary lung graft dysfunction could significantly attribute to ischemia-reperfusion lung injury (IRLI) during transplantation surgery. β2-adrenergic agonists were one of the bronchodilators that had been well-established in the management of asthma and chronic obstructive pulmonary disease (COPD) with anti-inflammatory potency. By applying the model of isolated rat lung, we evaluated the efficacy of short-acting β2-agonist inhalation to ameliorate ischemia-reperfusion damage. The experiment protocol was 180 min of global ischemia and then reperfusion for 60 min. In the β2-agonist inhalation group, aerosolized albuterol was administrated prior ischemia procedure. Increased weight ratios of wet to dry lung and microvascular permeability were characterized in the IRLI group. In contrast, pre-inhaled β2-agonist significantly mitigated the severity of pulmonary edema. Bronchoalveolar lavage from the β2-agonist group presented decreased leukocyte counts and cytokines production, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein 2 (MIP-2). Devastating oxidative stress was widely recognized during the ischemia-reperfusion process, while β2-agonist pretreatment revealed subsided H2O2, myeloperoxidase (MPO), and the cleavage of caspase-3. Western blotting from lung homogenates identified the blockade of NF-κB and MAPK activation in the β2-agonist inhalation group. Currently, there was no specific pharmacotherapy in IRLI management. Our results elucidated the protective effect of β2-agonist bronchodilator against ischemia-reperfusion induced oxidative stress, inflammation reaction, and pulmonary edema.