Effect of Subnormothermic Machine Perfusion on the Preservation of Vascularized Composite Allografts After Prolonged Warm Ischemia.

IF 5.3 2区医学 Q1 IMMUNOLOGY Transplantation Pub Date : 2024-11-01 Epub Date: 2024-10-22 DOI:10.1097/TP.0000000000005035

Laura Charlès, Irina Filz von Reiterdank, Hyshem H Lancia, Austin Alana Shamlou, Yanis Berkane, Ivy Rosales, Aebele B Mink van der Molen, J H Coert, Curtis L Cetrulo, Alexandre G Lellouch, Korkut Uygun

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Abstract

Background: Warm ischemia time (WIT) and ischemia-reperfusion injury are limiting factors for vascularized composite allograft (VCA) transplantation. Subnormothermic machine perfusion (SNMP) has demonstrated the potential to extend WIT in organ transplantation. This study evaluates the effect of SNMP on VCA viability after prolonged WIT.

Methods: Rat hindlimbs underwent WIT for 30, 45, 60, 120, 150, or 210 min, followed by 3-h SNMP. Monitoring of perfusion parameters and outflow determined the maximum WIT compatible with limb viability after SNMP. Thereafter, 2 groups were assessed: a control group with inbred transplantation (Txp) after 120 min of WIT and an experimental group that underwent WIT + SNMP + Txp. Graft appearance, blood gas, cytokine levels, and histology were assessed for 21 d.

Results: Based on potassium levels, the limit of WIT compatible with limb viability after SNMP is 120 min. Before this limit, SNMP reduces potassium and lactate levels of WIT grafts to the same level as fresh grafts. In vivo, the control group presented 80% graft necrosis, whereas the experimental group showed no necrosis, had better healing ( P = 0.0004), and reduced histological muscle injury ( P = 0.012). Results of blood analysis revealed lower lactate, potassium levels, and calcium levels ( P = 0.048) in the experimental group. Both groups presented an increase in interleukin (IL)-10 and IL-1b/IL-1F2 with a return to baseline after 7 to 14 d.

Conclusions: Our study establishes the limit of WIT compatible with VCA viability and demonstrates the effectiveness of SNMP in restoring a graft after WIT ex vivo and in vivo, locally and systemically.

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亚恒温机器灌注对长时间温缺血后血管化复合移植物保存的影响

背景：暖缺血时间（WIT）和缺血再灌注损伤是血管化复合异体移植物（VCA）移植的限制因素。亚低温机器灌注（SNMP）已证明有可能延长器官移植的WIT。本研究评估了 SNMP 对长时间 WIT 后 VCA 存活率的影响：方法：对大鼠后肢进行30、45、60、120、150或210分钟的WIT，然后进行3小时的SNMP。监测灌注参数和流出量确定与 SNMP 后肢体存活率相适应的最大 WIT。之后，对两组进行评估：WIT 120 分钟后进行近交系移植（Txp）的对照组和进行 WIT + SNMP + Txp 的实验组。21天后对移植物外观、血气、细胞因子水平和组织学进行评估：结果：根据血钾水平，在SNMP之后，WIT与肢体存活率相符的极限是120分钟。在此界限之前，SNMP 可将 WIT 移植肢体的钾和乳酸水平降至与新鲜移植肢体相同的水平。在体内，对照组出现了 80% 的移植物坏死，而实验组没有出现坏死，愈合情况更好（P = 0.0004），肌肉组织学损伤减少（P = 0.012）。血液分析结果显示，实验组的乳酸、钾和钙水平较低（P = 0.048）。两组的白细胞介素（IL）-10和IL-1b/IL-1F2都有所增加，但在7至14天后又恢复到基线水平：我们的研究确定了WIT与VCA存活率相容的限度，并证明了SNMP在体内外、局部和全身恢复WIT后移植物的有效性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplantation 医学-免疫学

CiteScore

8.50

自引率

11.30%

发文量

1906

审稿时长

1 months

期刊介绍： The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year. Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal. Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed. The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.