4. a1-Anti-trypsin improves function of porcine donor lungs during ex-vivo lung perfusion
J Heart Lung Transplant. 2017 Oct 2. pii: S1053-2498(17)32034-X. doi: 10.1016/j.healun.2017.09.019. [Epub ahead of print]
Lin H1, Chen M1, Tian F1, Tikkanen J1, Ding L1, Andrew Cheung HY1, Nakajima D1, Wang Z1, Mariscal A1, Hwang D1, Cypel M1, Keshavjee S1, Liu M2. ( Department of Surgery and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address:firstname.lastname@example.org.
Ex-vivo lung perfusion (EVLP), a technique for donor lung assessment, also represents a platform for donor lung repair and immunomodulation. α1-Anti-trypsin (A1AT), a medication used to treat emphysema in A1AT-deficient patients, has anti-inflammatory properties and has been shown to attenuate ischemia-reperfusion injury in rat and pig lung transplants. The objective of this study was to determine whether administration of A1AT during EVLP can improve donor lung quality after prolonged hypothermic preservation.
Pig donor lungs were retrieved, preserved at 4°C for 24 hours, and then subjected to normothermic EVLP for 12 hours using the Toronto protocol. The treatment group (n = 6) received 3 mg/ml A1AT (Zemaira) in the EVLP perfusate, acellular Steen solution. The control group (n = 6) was perfused with Steen solution only. Physiologic functions and gas exchange were measured hourly. Pulmonary edema, lung injury, apoptosis and inflammatory mediators were evaluated in lung tissues and perfusate.
A1AT treatment significantly reduced pulmonary arterial pressure, pulmonary vascular resistance and airway pressure changes from the baseline when compared with controls. A1AT treatment significantly improved both dynamic and static pulmonary compliance, and change in partial pressure of oxygen (ΔPO2) between the left atrium and the pulmonary artery. Furthermore, A1AT treatment also significantly reduced pulmonary edema (wet-to-dry ratio), pulmonary cell apoptosis and pro-inflammatory cytokine levels (interleukin-1α and -8) in the perfusate.
Treatment of 24-hour-preserved pig donor lungs with A1AT during EVLP resulted in improved physiologic function, reduced pulmonary edema and inflammation and decreased cell death. Our findings suggest that treatment of donor lungs during EVLP with A1AT is a promising strategy to attenuate early lung injury and improve donor lung function before lung transplantation.
Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
KEYWORDS: anti-apoptosis; anti-inflammation; donor organ repair; lung transplant; pre-clinical studies. PMID: 29153638 DOI:10.1016/j.healun.2017.09.019