Benefit of prophylactic bronchodilator withβ2 adrenergic agonist in ischemia-reperfusion-induced lung injury

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-actingβ2-agonist inhalation to ameliorate ischemia-reperfusion damage.The experiment protocol was 180 min of global ischemia and then reperfusion for 60 min.In theβ2-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-inhaledβ2-agonist significantly mitigated the severity of pulmonary edema.Bronchoalveolar lavage from theβ2-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,whileβ2-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 theβ2-agonist inhalation group.Currently,there was no specific pharmacotherapy in IRLI management.Our results elucidated the protective effect ofβ2-agonist bronchodilator against ischemia-reperfusion induced oxidative stress,inflammation reaction,and pulmonary edema.