Novel Dynamic Organ Storage System Enhances Liver Graft Function in a Porcine Donation After Circulatory Death Model.

IF 3.1 3区 医学 Q2 ENGINEERING, BIOMEDICAL
Yutaka Shishido, Kaitlyn M Tracy, Mark Petrovic, TiOluwanimi Adesanya, Avery K Fortier, Kimya Raietparvar, Gabriella A Glomp, Elizabeth Simonds, Timothy R Harris, Victoria Simon, William D Tucker, Brandon Petree, Michael Cortelli, Nancy L Cardwell, Christian Crannell, Jiancong Liang, Alexandria C Murphy, Blanche L Fields, Melanie McReynolds, Caitlin T Demarest, Rei Ukita, Michael Rizzari, Martin Montenovo, Joseph F Magliocca, Seth J Karp, M Ameen Rauf, Ashish S Shah, Matthew Bacchetta
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Abstract

Donation after circulatory death (DCD) livers face increased risks of critical complications when preserved with static cold storage (SCS). Although machine perfusion (MP) may mitigate these risks, its cost and logistical complexity limit widespread application. We developed the Dynamic Organ Storage System (DOSS), which delivers oxygenated perfusate at 10°C with minimal electrical power requirement and allows real-time effluent sampling in a portable cooler. In a porcine DCD model, livers were preserved using DOSS or SCS for 10 hours and evaluated with 4 hours of normothermic MP, with n = 5 per group. After 4 hours of normothermic MP, the DOSS group demonstrated significantly lower perfusate lactate (p = 0.023), increased perfusate fibrinogen (p = 0.005), higher oxygen consumption (p = 0.018), greater bile production (p = 0.013), higher bile bicarbonate levels (p = 0.035) and bile/perfusate sodium ratio (p = 0.002), and lower hepatic arterial resistance after phenylephrine administration (p = 0.018). Histological analysis showed lower apoptotic markers in DOSS-preserved livers, with fewer cleaved caspase-3 (p = 0.039) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL; p = 0.009) positive cells. These findings suggest that DOSS can enhance DCD allograft function during transport, offering potential clinical benefits and contributing to the expansion of the donor pool.

新型动态器官储存系统增强猪循环死亡模型捐献肝移植功能。
在循环死亡(DCD)后捐献的肝脏在静态冷库(SCS)保存时面临严重并发症的风险增加。虽然机器灌注(MP)可以减轻这些风险,但其成本和物流复杂性限制了其广泛应用。我们开发了动态器官存储系统(DOSS),该系统在10°C下以最小的电力需求提供含氧灌注液,并允许在便携式冷却器中进行实时流出取样。在猪DCD模型中,使用DOSS或SCS保存肝脏10小时,并使用4小时的恒温MP进行评估,每组n = 5。在等温MP治疗4小时后,DOSS组表现为灌注乳酸显著降低(p = 0.023),灌注纤维蛋白原显著升高(p = 0.005),耗氧量显著升高(p = 0.018),胆汁生成显著增加(p = 0.013),胆汁碳酸氢盐水平显著升高(p = 0.035),胆汁/灌注钠比显著升高(p = 0.002),给药后肝动脉阻力显著降低(p = 0.018)。组织学分析显示,doss保存的肝脏中凋亡标志物较低,caspase-3裂解(p = 0.039)和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸镍端标记(TUNEL;P = 0.009)阳性细胞。这些发现表明,DOSS可以增强DCD同种异体移植物在运输过程中的功能,提供潜在的临床益处,并有助于扩大供体池。
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
ASAIO Journal
ASAIO Journal 医学-工程:生物医学
CiteScore
6.60
自引率
7.10%
发文量
651
审稿时长
4-8 weeks
期刊介绍: ASAIO Journal is in the forefront of artificial organ research and development. On the cutting edge of innovative technology, it features peer-reviewed articles of the highest quality that describe research, development, the most recent advances in the design of artificial organ devices and findings from initial testing. Bimonthly, the ASAIO Journal features state-of-the-art investigations, laboratory and clinical trials, and discussions and opinions from experts around the world. The official publication of the American Society for Artificial Internal Organs.
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