Gradual rewarming with a hemoglobin-based oxygen carrier improves viability of donation after circulatory death in rat livers.

Frontiers in transplantation Pub Date : 2024-07-01 eCollection Date: 2024-01-01 DOI:10.3389/frtra.2024.1353124
Paria Mahboub, Mohamed Aburawi, O Sila Ozgur, Casie Pendexter, Stephanie Cronin, Florence Min Lin, Rohil Jain, Murat N Karabacak, Negin Karimian, Shannon N Tessier, James F Markmann, Heidi Yeh, Korkut Uygun
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Abstract

Background: Donation after circulatory death (DCD) grafts are vital for increasing available donor organs. Gradual rewarming during machine perfusion has proven effective in mitigating reperfusion injury and enhancing graft quality. Limited data exist on artificial oxygen carriers as an effective solution to meet the increasing metabolic demand with temperature changes. The aim of the present study was to assess the efficacy and safety of utilizing a hemoglobin-based oxygen carrier (HBOC) during the gradual rewarming of DCD rat livers.

Methods: Liver grafts were procured after 30 min of warm ischemia. The effect of 90 min of oxygenated rewarming perfusion from ice cold temperatures (4 °C) to 37 °C with HBOC after cold storage was evaluated and the results were compared with cold storage alone. Reperfusion at 37 °C was performed to assess the post-preservation recovery.

Results: Gradual rewarming with HBOC significantly enhanced recovery, demonstrated by markedly lower lactate levels and reduced vascular resistance compared to cold-stored liver grafts. Increased bile production in the HBOC group was noted, indicating improved liver function and bile synthesis capacity. Histological examination showed reduced cellular damage and better tissue preservation in the HBOC-treated livers compared to those subjected to cold storage alone.

Conclusion: This study suggests the safety of using HBOC during rewarming perfusion of rat livers as no harmful effect was detected. Furthermore, the viability assessment indicated improvement in graft function.

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使用基于血红蛋白的氧气载体逐步复温可提高大鼠肝脏循环死亡后的捐献存活率。
背景:循环死亡后捐献(DCD)移植物对于增加可用的捐献器官至关重要。事实证明,在机器灌注过程中逐步复温可有效减轻再灌注损伤并提高移植物质量。人工氧载体是满足随温度变化而增加的新陈代谢需求的有效解决方案,但这方面的数据有限。本研究旨在评估在 DCD 大鼠肝脏逐渐回温过程中使用基于血红蛋白的氧气载体(HBOC)的有效性和安全性:方法:大鼠肝脏在温缺血 30 分钟后移植。评估了冷藏后使用 HBOC 从冰冷温度(4 °C)到 37 °C进行 90 分钟氧复温灌注的效果,并将结果与单独冷藏进行了比较。在 37 °C下进行再灌注以评估保存后的恢复情况:结果:与冷藏肝脏移植物相比,用HBOC逐渐回温能显著促进恢复,表现为乳酸水平明显降低,血管阻力降低。HBOC组胆汁分泌增加,表明肝功能和胆汁合成能力得到改善。组织学检查显示,与单独冷藏的肝脏相比,经 HBOC 处理的肝脏细胞损伤减少,组织保存更好:这项研究表明,在对大鼠肝脏进行复温灌注时使用 HBOC 是安全的,因为没有发现有害影响。此外,存活率评估表明移植物功能有所改善。
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