Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion.
Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion.
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DOI：
10.1097/txd.0000000000001390
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发表时间：
2022-11
影响因子：
2.3
通讯作者：
中科院分区：
文献类型：
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成功的肠移植目前受到移植物在获取和储存过程中发生的损伤的阻碍，这有助于术后脓毒症和同种异体移植物排斥。改进的移植物保存可以扩大可移植的移植物数量并提高移植后的结果。上级移植结果最近已在使用机器灌注保存肝脏的临床试验中得到证实。我们假设可以实现肠同种异体移植物的机器灌注保存，并允许在猪模型中移植。使用平移猪模型，我们开发了一种用于肠灌注的装置。在器官获取时收集肠道样品，并在6小时的机器灌注后进行大体和组织学评价，每小时对灌注液进行一次化学检查，并用于方案优化。移植后，猪受体的身体活动，全身血液参数，和生命体征进行了监测2天前处死。在初始方案开发（第1代，n = 8移植物）中，测量了多种代谢、电解质和酸碱紊乱。这些因素与移植物和肠系膜水肿和管腔出血一致，并通过增加透析来解决。在随后的方案（第2代，n = 9移植物）中，观察到空肠和回肠灌注差异，导致回肠缺血的大体证据。血管扩张药物的改良增强了回肠灌注（第3代，n = 4移植物）。我们报告了2例经机器灌注的猪小肠移植成功，术后临床和大体证据显示肠功能正常。本研究报告了猪小肠机械灌注保存技术的发展和优化，以及同种异体小肠移植的成功。
Successful intestinal transplantation is currently hindered by graft injury that occurs during procurement and storage, which contributes to postoperative sepsis and allograft rejection. Improved graft preservation may expand transplantable graft numbers and enhance posttransplant outcomes. Superior transplant outcomes have recently been demonstrated in clinical trials using machine perfusion to preserve the liver. We hypothesized that machine perfusion preservation of intestinal allografts could be achieved and allow for transplantation in a porcine model. Using a translational porcine model, we developed a device for intestinal perfusion. Intestinal samples were collected at the time of organ procurement, and after 6 h of machine perfusion for gross and histologic evaluation, hourly chemistry panels were performed on the perfusate and were used for protocol optimization. Following transplantation, porcine recipient physical activity, systemic blood parameters, and vital signs were monitored for 2 d before sacrifice. In initial protocol development (generation 1, n = 8 grafts), multiple metabolic, electrolyte, and acid-base derangements were measured. These factors coincided with graft and mesenteric edema and luminal hemorrhage and were addressed with the addition of dialysis. In the subsequent protocol (generation 2, n = 9 grafts), differential jejunum and ileum perfusion were observed resulting in gross evidence of ileal ischemia. Modifications in vasodilating medications enhanced ileal perfusion (generation 3, n = 4 grafts). We report successful transplantation of 2 porcine intestinal allografts after machine perfusion with postoperative clinical and gross evidence of normal gut function. This study reports development and optimization of machine perfusion preservation of small intestine and successful transplantation of intestinal allografts in a porcine model.