ArticleThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2018
Preservation with α
Article in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Targeting the proline-glycine-proline-protease feed-forward loop attenuates primary graft dysfunction after lung transplantation.Frontiers in immunology · 2026Article
- Protective effects of neutrophil serine protease inhibition against ischemia-reperfusion injury in lung or heart transplantation.The FEBS journal · 2025Review
- Organ preservation: current limitations and optimization approaches.Frontiers in medicine · 2025Review
- Primary graft dysfunction following lung transplantation: From pathogenesis to future frontiers.World journal of transplantation · 2023Review
- Preservation solution Custodiol containing human alpha-1-antitrypsin improves graft recovery after prolonged cold ischemic storage in a rat model of heart transplantation.Frontiers in immunology · 2023Article
- Protective α1-antitrypsin effects in autoimmune vasculitis are compromised by methionine oxidation.The Journal of clinical investigation · 2022Article
- α1-Antitrypsin attenuates acute rejection of orthotopic murine lung allografts.Respiratory research · 2021Article
- Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation.Scientific reports · 2021Article
- Boosted Pro-Inflammatory Activity in Human PBMCs by Lipopolysaccharide and SARS-CoV-2 Spike Protein Is Regulated by α-1 Antitrypsin.International journal of molecular sciences · 2021Article
- Review 2: Primary graft dysfunction after lung transplant-pathophysiology, clinical considerations and therapeutic targets.Journal of anesthesia · 2020Review
- Long non-coding RNA X-inactive specific transcript silencing ameliorates primary graft dysfunction following lung transplantation through microRNA-21-dependent mechanism.EBioMedicine · 2020Article
- Endothelial Microvesicles Induce Pulmonary Vascular Leakage and Lung Injury During Sepsis.Frontiers in cell and developmental biology · 2020Article
- Three Is Better than One: An Improved Multiple-Hit Model of Primary Graft Dysfunction.American journal of respiratory cell and molecular biology · 2019Article
- Premedication with a cathepsin C inhibitor alleviates early primary graft dysfunction in mouse recipients after lung transplantation.Scientific reports · 2019Article
- Alpha-1 Antitrypsin Attenuates Acute Lung Allograft Injury in a Rat Lung Transplant Model.Transplantation direct · 2019Article
- Early Graft Dysfunction after Lung Transplantation.Current pulmonology reports · 2018Article
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVascular damage and primary graft dysfunction increase with prolonged preservation times of transplanted donor lungs. Hence, storage and conservation of donated lungs in protein-free, dextran-containing electrolyte solutions, like Perfadex, is limited to about 6 hours. We hypothesized that transplanted lungs are protected against neutrophil-mediated proteolytic damage by adding α
methodsA realistic clinically oriented murine model of lung transplantation was used to simulate the ischemia-reperfusion process. Lung grafts were stored at 4°C in Perfadex solution supplemented with AAT or an AAT mutant devoid of elastase-inhibiting activity for 18 hours. We examined wild-type and proteinase 3/neutrophil elastase (PR3/NE) double-deficient mice as graft recipients. Gas exchange function and infiltrating neutrophils of the transplanted lung, as well as protein content and neutrophil numbers in the bronchoalveolar lavage fluid, were determined.
resultsAAT as a supplement to Perfadex reduced the extent of primary graft dysfunction and early neutrophil responses after extended storage for 18 hours at 4°C and 4-hour reperfusion in the recipients. Double-knockout recipients that lack elastase-like activities in neutrophils were also protected from early reperfusion injury, but not lung grafts that were perfused with a reactive center mutant of AAT devoid of elastase-inhibiting activity.
conclusionsPR3 and NE, the principal targets of AAT, are major triggers of post-ischemic reperfusion damage. Their effective inhibition in the graft and recipient is a promising strategy for organ usage after storage for >6 hours.
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