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DOI: 10.1055/s-0043-115524
Ex-vivo-Lungenperfusion
Ex-vivo Lung PerfusionPublication History
Publication Date:
15 November 2018 (online)
Zusammenfassung
Die Lungentransplantation nahm ihren Ursprung Mitte des 20. Jahrhunderts, doch erst die Einführung des Ciclosporins 1981 brachte den entscheidenden Durchbruch, insbesondere das Langzeitüberleben der Patienten betreffend. Durch die derzeit zunehmende Inzidenz finaler Lungenerkrankungen kommt es jedoch zu einer steigenden Diskrepanz zwischen Organempfängern und Organspendern. Dieses Problem adressierend, befasst sich ein globaler Forschungsfokus mit der Entwicklung und Etablierung der sogenannten Ex-vivo-Lungenperfusion (EVLP), die entgegen des Goldstandards der hypothermen, statischen Organkonservierung die in das EVLP eingespannte Lunge körperwarm perfundiert und beatmet. Hierbei werden 3 wesentliche Strategien zur Erweiterung des Spenderpools verfolgt – sowohl der Einsatz bei sogenannten „Donation after cardiac Death“ mit der Möglichkeit der Reevaluation der in das EVLP implantierten Lunge als auch die Langzeit-EVLP-Anwendung mit der diagnoseabhängigen Therapie suboptimaler Lungen soll für die Konversion nicht transplantabler in transplantable Lungen genutzt werden. Zudem dient das portable EVLP-System der Eskalation der geografischen Flexibilität im Rahmen des Spendermanagements und ist mit der Minimierung der kalten Ischämiezeit assoziiert. Zwar bestehen die EVLP-Systeme aus den gleichen Komponenten, doch ergeben sich aus ihnen eine Vielzahl an Möglichkeiten, das jeweilige EVLP-Protokoll je nach Indikation gestalten zu können. Die Datenanalysen der EVLP-Systeme bestätigen deren Applikation im Rahmen der humanen Lungentransplantation als opportun. Es kommt zu einem reduzierten Ischämie-/Reperfusionsschaden, in dessen Folge sich sowohl die Gasaustauschleistung der Lunge im EVLP als auch der PGD-Grad (PGD: Primary Graft Dysfunction) der Organempfänger im Vergleich zur hypothermen statischen Konservierung signifikant verbessert. Basierend auf diesen Ergebnissen und der Möglichkeit der individuellen Adaptation des EVLP-Protkolls ergeben sich neben der transplantationsassoziierten Anwendung weitere interessante Einsatzgebiete, wie beispielsweise der Infektions- und Tumortherapie, aber auch der Immunmodulation.
Abstract
The surgical procedure of lung transplantation dates back to the middle of the 20th century. However, its use in standard clinical practice came much later in 1981, with the introduction of Ciclosporin providing the decisive breakthrough for the long-term survival of patients. The increasing incidence of end-stage or terminal lung diseases has resulted in a growing discrepancy between the number of available organs and patients on transplant waiting lists. To address this problem, researchers worldwide are now focusing on ex-vivo lung perfusion (EVLP), which, in contrast to the current gold standard of hypothermic static organ preservation, perfuses and ventilates the explanted lung at body temperature. In this way, three main strategies to expand the donor pool can be followed. The use of EVLP for organ donation after cardiac death allows re-evaluation of the donor lung before transplantation, while longer term EVLP enables diagnosis-related therapy of suboptimal lungs, both with the aim of increasing the number of transplantable lungs. Furthermore, portable EVLP systems can increase geographical flexibility for donor management and minimize cold ischemic times. While all EVLP-systems consist of comparable components, there is a wide range of possibilities to design individually adapted EVLP protocols. Data analyses on the use of EVLP systems highlight their advantages for human lung transplantation. Fewer ischemic/reperfusion injuries were observed, which subsequently led to better gas exchange and also significantly lower primary graft dysfunction (PDG) scores compared with standard preserved lungs. Based on these promising results and the possibility to individually adapt EVLP protocols for a variety of settings, EVLP appears to hold significant potential not only for transplantation medicine, but also for a range of other applications, such as infection therapy, tumor therapy and immunomodulation.
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