Purpose: Even though lung transplantation has been the effective treatment for patients with end-stage lung diseases, pulmonary ischemia reperfusion (IR) injury continues to be the major cause of primary graft dysfunction and early mortality after lung transplantation and contributes to the development of acute rejection and chronic graft dysfunction. No effective drugs exist clinically for its treatment. Alpha 1-antitrypsin (A1AT) is a protease inhibitor for A1AT deficiency replacement therapy. We have recently shown that it has anti-inflammation and anti-apoptosis effects in a simulated pulmonary IR cell culture model. Thus, we tested whether A1AT can prevent pulmonary IR injury in vivo.
Materials and Methods: A rat pulmonary ischemia reperfusion model was used by clamping the left hilum for 90 min and followed by reperfusion for 2 h. 50 mg/kg A1AT (Zemaira®, Csl behring, USA) was intravenously administrated 30 min before ischemia. After 2 h reperfusion, the left lung was ventilated with oxygen for 5 min by clamping the right hilum. Arterial blood gases and left lung mechanics were assessed. The left lung tissue and serum were collected for wet/dry ratio, histology, apoptosis and inflammatory mediator assessments.
Results: Compared with saline control group, A1AT treatment significantly increased the lung oxygenation function after IR (528.8 ± 23.3 vs. 353.1 ± 59.2 mmHg, p=0.025). Lung compliance in A1AT group was significantly improved (0.191 ± 0.008 vs. 0.136 ± 0.019 ml/cmH2O, p=0.040). A1AT also prevented IR induced edema, neutrophil infiltration and activation, and lung epithelial cell apoptosis. IR induced systemic inflammatory mediators (IL-1Α, TNFΑ, MCP-1, IL-12p70 and IL-4) were significantly reduced by A1AT (P<0.05).
Conclusion: These results, together with our recent cell biological studies, indicate that A1AT may prevent pulmonary IR induced acute lung injury, through anti-inflammation and anti-apoptotic effects. A large animal lung transplantation model and a clinical trial are under consideration, in order to use A1AT to prevent IR injury in lung transplantation.
To cite this abstract in AMA style:Zhao J, Gao W, Cypel M, Keshavjee S, Liu M. Alpha 1-Antitrypsin (A1AT) Prevents Pulmonary Ischemia Reperfusion Injury in Rats [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/alpha-1-antitrypsin-a1at-prevents-pulmonary-ischemia-reperfusion-injury-in-rats/. Accessed October 27, 2020.
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