1 Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est, Créteil, France. 2 Institut Mondor Recherche Biomédicale (IMRB), Université Paris-Est, Créteil, France. 3 Service de Réanimation Digestive, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est, Créteil, France. 4 Service d'Anatomopathologie, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est, Créteil, France. 5 Service d'Hépatologie, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est, Créteil, France. 6 INSERM, Univ Rennes, INRA, Nutrition Metabolisms and Cancer (NuMeCan), Rennes, France. 7 Biopredic International, Rennes, France.
Transplantation. 2017 Jul;101(7):e205-e213. doi: 10.1097/TP.0000000000001764.
Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model.
Cardiac arrest was induced in female large white pigs by intravenous injection of potassium chloride. After 60 minutes of WI, livers were flushed in situ with histidine-tryptophan-ketoglutarate and subsequently preserved either by simple cold storage (WI-SCS group) or HMP (WI-HMP group) using Belzer-MPS solution. Liver grafts procured from heart-beating donors and preserved by SCS served as controls. After 4 hours of preservation, all livers were transplanted.
All recipients in WI-SCS group died within 6 hours after transplantation. In contrast, the HMP device fully protected the liver against lethal ischemia/reperfusion injury, allowing 100% survival rate. A postreperfusion syndrome was observed in all animals of the WI-SCS group but none of the control or WI-HMP groups. After reperfusion, HMP-preserved livers functioned better and showed less hepatocellular and endothelial cell injury, in agreement with better-preserved liver histology relative to WI-SCS group. In addition to improved energy metabolism, this protective effect was associated with an attenuation of inflammatory response, oxidative load, endoplasmic reticulum stress, mitochondrial damage, and apoptosis.
This study demonstrates for the first time the efficacy of the HMP Airdrive system to protect liver grafts from lethal ischemic damage before transplantation in a clinically relevant DCD model.
控制与循环死亡后捐赠（DCD）相关的热缺血（WI）损伤将显著增加肝移植的供体池。我们旨在使用大型动物模型确定新型充氧和低温机器灌注设备（HMP Airdrive 系统）是否可以改善来自 DCD 的肝脏质量。
通过静脉注射氯化钾诱导雌性大白猪心脏骤停。WI 60 分钟后，用组氨酸-色氨酸-酮戊二酸原位冲洗肝脏，然后使用 Belzer-MPS 溶液进行简单冷藏（WI-SCS 组）或 HMP（WI-HMP 组）保存。来自心跳供体并通过 SCS 保存的肝移植物作为对照。保存 4 小时后，所有肝脏均进行移植。
WI-SCS 组的所有受者在移植后 6 小时内均死亡。相比之下，HMP 设备完全防止了致命的缺血/再灌注损伤，使 100%的存活率成为可能。在 WI-SCS 组的所有动物中均观察到再灌注后综合征，但在对照组或 WI-HMP 组中均未观察到。再灌注后，HMP 保存的肝脏功能更好，肝细胞和内皮细胞损伤较少，与 WI-SCS 组相比，肝组织学保存更好。除了改善能量代谢外，这种保护作用还与炎症反应、氧化应激、内质网应激、线粒体损伤和细胞凋亡的减轻有关。
本研究首次证明了 HMP Airdrive 系统在临床相关 DCD 模型中在移植前保护肝移植物免受致命缺血损伤的有效性。
