Benefit of prophylactic bronchodilator with β2 adrenergic agonist in ischemia-reperfusion-induced lung injury
  • CHEN-LIANG TSAI1, YU-HUEI LIN2, CHIH-YING CHANGCHIEN3, CHIH-FENG CHIAN1,#,*, CHI-HUEI CHIANG4,#,*
1 Division of Pulmonary and Critical Care, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan
2 Post-Baccalaureate Program in Nursing, College of Nursing, Taipei Medical University, Taipei, 110, Taiwan
3 Department of General Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan
4 Division of Pulmonary Immunology and Infectious Diseases, Chest Department, Taipei Veterans General Hospital, Taipei, 112, Taiwan
* Address correspondence to: Chi-Huei Chiang, chiang1990@gmail.com; Chih-Feng Chian, sonice3982@gmail.com
# These authors contributed equally to this work
(This article belongs to this Special Issue:Cellular Biomechanics in Health and Diseases)
Received 15 September 2020; Accepted 24 February 2021 ; Published online 21 April 2021
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.
Keywords
Ischemia-reperfusion lung injury, β2-adrenergic agonist, Bronchodilator, Lung transplantation