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实验性失血性休克中基于血红蛋白的氧载体的兽医观点:来自兔模型的见解

Veterinary Perspectives on Hemoglobin-Based Oxygen Carriers in Experimental Hemorrhagic Shock: Insights from Rabbit Models.

作者信息

Dandea Ștefania-Mădălina, Hașaș Alina-Diana, Toma Vlad-Alexandru, Lehene Maria, Scurtu Florina, Peștean Cosmin Petru, Codea Răzvan-Andrei, Bel Lucia-Victoria, Melega Iulia, Silaghi-Dumitrescu Radu, Sevastre Bogdan

机构信息

Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania.

Department of Molecular Biology and Biotechnology, Babeș-Bolyai University, 400084 Cluj-Napoca, Romania.

出版信息

Vet Sci. 2025 May 16;12(5):485. doi: 10.3390/vetsci12050485.

Abstract

Hemoglobin-based oxygen carriers (HBOCs) represent a promising alternative to traditional blood transfusions, offering the advantages of extended shelf life and avoiding blood compatibility limitations and infection risks. Positive effects of hemoglobin-based oxygen carriers (HBOCs) on hemorrhagic shock have been researched across various animal species, including swine, rats, rabbits, guinea pigs, and dogs. As previously described, HBOCs based on ovine hemoglobin display better efficiency in the context of hemorrhagic shock compared to those based on the more commonly used bovine hemoglobin. This was evidenced through higher survival rates and more favorable histopathological and immunological outcomes. The vascular effects of ovine hemoglobin polymerized with glutaraldehyde exposure included the absence of hypertension, minimal endothelial damage with slight alterations in inducible nitric oxide synthase (iNOS), and reduced vascular inflammation mediated by interleukin-10 (IL-10). Ovine hemoglobin has emerged as a particularly promising raw material for the development of HBOCs, surpassing bovine and human hemoglobin due to its advantages in availability and efficacy. Furthermore, reducing oxidative stress by polymerizing hemoglobin with glutaraldehyde is most effective with ovine hemoglobin compared to bovine hemoglobin. This study evaluates the effectiveness of ovine hemoglobin polymerized with glutaraldehyde in managing hemorrhagic shock in rabbits, with a focus on its ability to maintain blood pressure, support oxygen transport, and assess potential systemic and oxidative responses. Fifteen adult New Zealand white rabbits, divided into three equal groups, were included in this study: a negative control group transfused with colloid solutions, a positive control group treated with autotransfusion, and a group receiving HBOCs. All groups underwent a hemorrhagic shock protocol, with 40% of their total blood volume withdrawn under deep anesthesia, followed by transfusions 30 min later. Vital parameters, including invasive arterial blood pressure, heart rate, and end-tidal CO, were measured throughout the experimental procedures. Arterial blood gas samples were collected before the procedures, after hemorrhagic shock induction, and at the conclusion of the transfusion. In summary, HBOCs offer a promising solution for oxygen delivery, but their effects on blood chemistry, particularly CO and lactate levels, must be considered. Although no direct oxygenation issues were observed in experimental models, elevated CO levels and the interference of HBOCs with lactate measurements emphasize the importance of vigilant clinical monitoring. Polymerized hemoglobin provides a non-nephrotoxic alternative, but challenges persist in preventing nitric oxide scavenging and ensuring effective oxygen delivery.

摘要

基于血红蛋白的氧载体(HBOCs)是传统输血的一种有前景的替代方案,具有保质期延长的优点,且避免了血液相容性限制和感染风险。已在包括猪、大鼠、兔子、豚鼠和狗在内的各种动物物种中研究了基于血红蛋白的氧载体(HBOCs)对失血性休克的积极作用。如前所述,与基于更常用的牛血红蛋白的氧载体相比,基于羊血红蛋白的氧载体在失血性休克情况下显示出更高的效率。这通过更高的存活率以及更有利的组织病理学和免疫学结果得到证明。经戊二醛处理聚合的羊血红蛋白的血管效应包括无高血压、诱导型一氧化氮合酶(iNOS)仅有轻微改变导致的最小内皮损伤,以及由白细胞介素-10(IL-10)介导的血管炎症减轻。羊血红蛋白已成为开发基于血红蛋白的氧载体(HBOCs)特别有前景的原材料,因其在可用性和功效方面优于牛血红蛋白和人血红蛋白。此外,与牛血红蛋白相比,用戊二醛聚合血红蛋白以降低氧化应激对羊血红蛋白最为有效。本研究评估经戊二醛聚合的羊血红蛋白在处理兔子失血性休克中的有效性,重点关注其维持血压、支持氧运输的能力以及评估潜在的全身和氧化反应。本研究纳入了15只成年新西兰白兔,平均分为三组:输注胶体溶液的阴性对照组、自体输血治疗的阳性对照组和接受基于血红蛋白的氧载体(HBOCs)的组。所有组均采用失血性休克方案,在深度麻醉下抽取其总血容量的40%,30分钟后进行输血。在整个实验过程中测量重要参数,包括有创动脉血压、心率和呼气末二氧化碳。在操作前、失血性休克诱导后以及输血结束时采集动脉血气样本。总之,基于血红蛋白的氧载体(HBOCs)为氧输送提供了一个有前景的解决方案,但必须考虑它们对血液化学的影响,特别是二氧化碳和乳酸水平。尽管在实验模型中未观察到直接的氧合问题,但二氧化碳水平升高以及基于血红蛋白的氧载体(HBOCs)对乳酸测量的干扰强调了警惕临床监测的重要性。聚合血红蛋白提供了一种非肾毒性的替代方案,但在防止一氧化氮清除和确保有效氧输送方面仍存在挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf0/12116158/44f8de6da552/vetsci-12-00485-g001.jpg

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