Risk and recovery of outflow obstruction in living-related liver transplantation: The influence of liver perfusion on regeneration and outcome

活体肝移植中流出道梗阻的风险和恢复：肝脏灌注对再生和结局的影响

• 批准号: 56706278
• 负责人: Professor Dr. Heinz-Otto Peitgen
• 金额: --
• 依托单位: Fraunhofer-Institut für Digitale Medizin (MEVIS)
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/56706278?language=en
• 关键词: Risk; recovery; outflow; obstruction; living

Perfusion-related problems account for numerous complications after liver transplantation. Outflow obstruction represents one of the key surgical problems in adult living-related liver donation, as the donor liver has to be split into two hemi-livers and middle hepatic vein branches have to be transected. Insufficient drainage compromising liver function and leading to an impaired regeneration of the dependent territories is the consequence, increasing the risk for the patient by additional reduction of functional liver mass. Reduction of functional liver mass and impaired regeneration were prevented experimentally in rat model of extended liver resection by applying a vessel-oriented parenchyma preserving resection technique instead of the formerly used mass ligation technique. Recovery of the impaired drainage of outflow obstructed areas by vascularization of dilated sinusoids in combination with a remodeled liver architecture and an impaired regeneration was observed in a newly developed surgical model. These and other clinical and experimental observations lead to the hypothesis that focal outflow obstruction is the key event compromising the functional capacity and the regeneration of the dependent territories, suggesting a local regulation of liver regeneration. The first aim of this interdisciplinary project is the evaluation of the functional relevance of outflow obstruction in terms of liver function, regeneration, and revascularization employing the rat and woodchuck model. The second aim is to investigate the underlying mechanism and its pharmacological modulation. The third aim is to assess the biological importance of outflow obstruction not only in the model of liver resection but also after partial liver transplantation. Based on serial histological sections, software algorithms for automatic analysis and three-dimensional visualization of morphological data will be developed. This will lead to a deeper understanding of the regulatory influence of focally impaired liver perfusion not only on liver regeneration in terms of volume and vascular regeneration, but also in terms of the spatial distribution of molecular processes during the course of liver regeneration.

灌注相关问题是肝移植后众多并发症的原因。流出道阻塞是成人活体肝脏捐献中的关键手术问题之一，因为供体肝脏必须分成两个半肝脏，并且必须横断肝中静脉分支。引流不足会损害肝功能并导致附属区域再生受损，从而因功能性肝脏质量进一步减少而增加患者的风险。通过应用面向血管的实质保留切除技术而不是以前使用的质量结扎技术，在扩大肝脏切除的大鼠模型中实验性地防止了功能性肝脏质量的减少和再生受损。在新开发的手术模型中观察到，通过扩张的血窦的血管化结合重塑的肝脏结构，流出阻塞区域的引流受损的恢复和受损的再生。这些以及其他临床和实验观察结果得出这样的假设：局灶性流出阻塞是损害功能能力和附属区域再生的关键事件，这表明肝脏再生的局部调节。这个跨学科项目的首要目标是利用大鼠和土拨鼠模型评估流出阻塞在肝功能、再生和血运重建方面的功能相关性。第二个目标是研究潜在的机制及其药理调节。第三个目的是评估流出阻塞的生物学重要性，不仅在肝切除模型中而且在部分肝移植后。基于连续组织切片，将开发用于形态数据自动分析和三维可视化的软件算法。这将导致人们更深入地了解局部受损的肝脏灌注不仅对肝脏再生的体积和血管再生的调节影响，而且还对肝脏再生过程中分子过程的空间分布的影响。