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HBOC-201 在大鼠模型中离体逐步复温肾脏灌注中的疗效。

The efficacy of HBOC-201 in ex situ gradual rewarming kidney perfusion in a rat model.

机构信息

University Medical Center Groningen, Groningen, Netherlands.

Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

出版信息

Artif Organs. 2020 Jan;44(1):81-90. doi: 10.1111/aor.13534. Epub 2019 Aug 1.

Abstract

Gradual rewarming from hypothermic to normothermic is a novel perfusion modality with superior outcome to sudden rewarming to normothermic. However, the identification of an oxygen carrier that could function at a temperature range from 4 to 7°C or whether it is necessary to use oxygen carrier during kidney rewarming, remains unresolved. This study was designed to test the use of a hemoglobin-based oxygen carrier (HBOC) during gradual kidney rewarming as an alternative to simple dissolved oxygen. In this study, 10 rat kidneys were randomly divided into the control and the HBOC group. In the control group, no oxygen carrier was used during rewarming perfusion and the perfusion solution was oxygenated only by applying diffused carbogen flow. The protocol mimicked a donor after circulatory death (DCD) kidney transplantation, where after 30 minutes warm ischemia and 120 minutes cold storage in University of Wisconsin solution, the DCD kidneys underwent gradual rewarming from 10 to 37°C during 90 minutes with or without HBOC. This was followed by 30 minutes of warm ischemia in room temperature to mimic the anastomosis time and 120 minutes of reperfusion at 37°C to mimic the early post-transplant state of the graft. The HBOC group demonstrated superior kidney function which was highlighted by higher ultrafiltrate production, better glomerular filtration rate and improved sodium reabsorption. There was no significant difference between the 2 groups regarding the hemodynamics, tissue injury, and adenosine triphosphate levels. In conclusion, this study suggests better renal function recovery in DCD kidneys after rewarming with HBOC compared to rewarming without an oxygen carrier.

摘要

从低体温逐渐复温到正常体温是一种新型的灌注方式,其结果优于突然复温到正常体温。然而,能够在 4 至 7°C 温度范围内发挥作用的氧载体的鉴定,或者在肾脏复温过程中是否有必要使用氧载体,仍然没有得到解决。本研究旨在测试在逐渐复温过程中使用血红蛋白基氧载体(HBOC)作为溶解氧的替代物。在这项研究中,10 个大鼠肾脏被随机分为对照组和 HBOC 组。在对照组中,复温灌注过程中不使用氧载体,仅通过施加弥散碳氧流使灌注液氧合。该方案模拟了循环死亡(DCD)供体肾移植后的情况,在 30 分钟热缺血和在威斯康星大学溶液中冷保存 120 分钟后,DCD 肾脏在 90 分钟内从 10°C 逐渐复温到 37°C,期间有无 HBOC。这之后在室温下进行 30 分钟的热缺血,以模拟吻合时间,在 37°C 下进行 120 分钟的再灌注,以模拟移植物的早期移植后状态。HBOC 组表现出更好的肾功能,其特征是超滤量更高、肾小球滤过率更好和钠吸收改善。两组之间的血流动力学、组织损伤和三磷酸腺苷水平没有显著差异。总之,与没有氧载体的复温相比,DCD 肾脏在 HBOC 复温后肾功能恢复更好。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20cc/6916591/4a043da18fc7/AOR-44-81-g001.jpg

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