Mueller A R, Platz K P, Haak M, Undi H, Müller C, Köttgen E, Weidemann H, Neuhaus P
Department of Surgery, Virchow Klinikum, Humboldt University of Berlin, Germany.
Transplantation. 1996 Oct 27;62(8):1118-26. doi: 10.1097/00007890-199610270-00017.
Poor initial graft function may increase postoperative morbidity including the risk of early allograft rejection. Various mediators, including immunostimulatory cytokines, may be released during reperfusion in relation to the extent of preservation and reperfusion injury. For this purpose, 81 patients with 85 liver transplants were monitored for cytokines, adhesion molecules, extracellular matrix (ECM) parameters, and neopterin at predefined time-points during and after transplantation. To estimate the origin of cytokine release, blood was obtained central and hepatic venously for the first 48 hr after reperfusion and subsequently from a peripheral vein. One-year patient survival was 88.9%; no relation to initial graft function was observed. Poor initial graft function failed to increase the risk for subsequent infectious complications but was associated with an increased risk of early allograft rejection. The incidence of steroid-resistant rejection was significantly increased in patients with poor initial graft function (35.7% versus 12.7% in patients with good and moderate initial graft function; P < or = 0.05). Various cytokines, adhesion molecules, and ECM parameters including sTNF-RII, sIL-2R, IL-8, IL-10, sVCAM-1, E-selectin, hyaluronic acid, sialic acid, and laminin correlated significantly with the extent of preservation and reperfusion injury. Although none of these parameters was more appropriate in determining the extent of preservation and reperfusion injury than currently established parameters (AST, ALT, and color and amount of bile production), the combined increase in these parameters may not only promote tissue repair but may also perpetuate liver allograft injury and thereby cause significant morbidity. Besides cytokines and adhesion molecules, the ECM may play a pivotal role in determining repair or ongoing tissue injury. Ongoing changes at the microvasculature and basement membrane may result in an increase of local and circulating cytokines and adhesion molecules, which increase the risk of subsequent early allograft rejection. Furthermore, the increase in sTNF-RII, E-selectin, and laminin during reperfusion was predictive of subsequent development of acute allograft rejection. These observations may be of value for further strategies to decrease reperfusion injury and prevent early allograft rejection.
移植肝初期功能不良可能会增加术后发病率，包括早期移植肝排斥反应的风险。在再灌注过程中，包括免疫刺激细胞因子在内的多种介质可能会因保存和再灌注损伤的程度而释放。为此，对81例接受85次肝移植的患者在移植期间及移植后的预定时间点监测细胞因子、黏附分子、细胞外基质（ECM）参数和新蝶呤。为了评估细胞因子释放的来源，在再灌注后的头48小时从中心静脉和肝静脉采集血液，随后从外周静脉采集。患者1年生存率为88.9%；未观察到与移植肝初期功能的相关性。移植肝初期功能不良并未增加随后感染并发症的风险，但与早期移植肝排斥反应风险增加相关。移植肝初期功能不良的患者中，类固醇抵抗性排斥反应的发生率显著增加（初期功能良好和中等的患者中分别为12.7%和35.7%；P≤0.05）。包括可溶性肿瘤坏死因子受体II（sTNF-RII）、可溶性白细胞介素-2受体（sIL-2R）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、可溶性血管细胞黏附分子-1（sVCAM-1）、E-选择素、透明质酸、唾液酸和层粘连蛋白在内的多种细胞因子、黏附分子和ECM参数与保存和再灌注损伤的程度显著相关。尽管这些参数中没有一个在确定保存和再灌注损伤程度方面比目前已确立的参数（天冬氨酸转氨酶、丙氨酸转氨酶以及胆汁产生的颜色和量）更合适，但这些参数的联合升高不仅可能促进组织修复，还可能使移植肝损伤持续存在，从而导致严重的发病率。除了细胞因子和黏附分子外，ECM可能在决定修复或持续的组织损伤中起关键作用。微血管和基底膜的持续变化可能导致局部和循环中的细胞因子及黏附分子增加，从而增加随后早期移植肝排斥反应的风险。此外，再灌注期间sTNF-RII、E-选择素和层粘连蛋白的升高可预测随后急性移植肝排斥反应的发生。这些观察结果可能对减少再灌注损伤和预防早期移植肝排斥反应的进一步策略具有价值。
