Department of Surgery, Institut de Malalties Digestives I Metabòliques, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain.
Departments of Anesthesia, Hospital Clínic, University of Barcelona, Barcelona, Spain.
Liver Transpl. 2018 May;24(5):665-676. doi: 10.1002/lt.25013. Epub 2018 Apr 10.
Ischemic-type biliary lesions (ITBLs) arise most frequently after donation after circulatory death (DCD) liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug tissue plasminogen activator (TPA) as means to improve DCD liver graft quality and potentially avoid ITBL. Donor pigs were subjected to 1 hour of cardiac arrest (CA) and divided among 3 groups: no pre-arrest heparinization nor TPA during postmortem regional perfusion; no pre-arrest heparinization but TPA given during regional perfusion; and pre-arrest heparinization but no TPA during regional perfusion. In liver tissue sampled 1 hour after CA, fibrin deposition was not detected, even when heparin was not given prior to arrest. Although it was not useful to prevent microvascular clot formation, pre-arrest heparin did offer cytoprotective effects during CA and beyond, reflected in improved flows during regional perfusion and better biochemical, functional, and histological parameters during posttransplantation follow-up. In conclusion, this study demonstrates the lack of impact of TPA use in porcine DCD liver transplantation and adds to the controversy over whether the use of TPA in human DCD liver transplantation really offers any protective effect. On the other hand, when it is administered prior to CA, heparin does offer anti-inflammatory and other cytoprotective effects that help improve DCD liver graft quality. Liver Transplantation 24 665-676 2018 AASLD.
缺血型胆道病变（ITBL）在死后循环死亡（DCD）肝移植后最常发生，导致高发病率和移植物丢失。出于对这种并发症的担忧，许多 DCD 供体的移植物被丢弃。理论上，供体热缺血期间沉积的微血管血栓可能与 ITBL 的发病机制有关。在此，我们旨在评估肝素或纤维蛋白溶解药物组织纤溶酶原激活剂（tPA）的给药效果，以改善 DCD 肝移植物的质量，并可能避免 ITBL。供体猪经历 1 小时的心脏骤停（CA），并分为 3 组：死后区域性灌注期间无 CA 前肝素化或 tPA；无 CA 前肝素化但区域性灌注时给予 tPA；以及 CA 前肝素化但区域性灌注时无 tPA。在 CA 后 1 小时采集的肝组织中，即使在 CA 前未给予肝素，也未检测到纤维蛋白沉积。虽然它不能预防微血管血栓形成，但 CA 前肝素确实提供了 CA 期间和之后的细胞保护作用，反映在区域性灌注期间的流量改善和移植后随访期间的生化、功能和组织学参数更好。总之，本研究表明 tPA 在猪 DCD 肝移植中使用没有影响，并增加了关于 tPA 在人类 DCD 肝移植中是否真的提供任何保护作用的争议。另一方面，当在 CA 前给予时，肝素确实提供抗炎和其他细胞保护作用，有助于改善 DCD 肝移植物的质量。肝移植 24 665-676 2018 AASLD。
