Blood Substitutes

血液替代品
  • 文章类型: Journal Article
    氧气是生命所必需的,在维持正常生理功能和治疗疾病中起着关键的作用。已经研究并开发了基于血红蛋白的氧载体(HBOC),因为它们具有相似的携氧能力,可以替代氧气运输中的红细胞(RBC)。然而,HBOCs的应用受到血管活性的阻碍,氧化毒性,和相对较短的循环半衰期。随着纳米技术的进步,Hb封装,吸收,生物缀合,诱捕,和附着到纳米材料已被用于制备纳米材料相关的HBOCs,以解决这些挑战,并在一些生物医学和治疗环境中的应用。本文就该类纳米材料相关HBOCs在失血性休克领域的研究进展作一综述。缺血性卒中,癌症,伤口愈合,并对未来的研究方向进行了推测。与纳米材料相关的HBOCs的进步有望在血液替代品方面取得重大突破,使其广泛用于临床疾病的治疗。
    Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases.
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  • 文章类型: Journal Article
    背景:本研究旨在阐明采用人工血管的主动脉弓包合技术治疗急性A型主动脉夹层(ATAAD)的方法学和疗效评估。
    方法:我们对18例患者(男11例,女7例,平均年龄:56.2±8.6岁),在2020年6月至2022年10月期间,诊断为ATAAD,并使用人工血管“纳入物”进行了全主动脉弓置换术(TAAR)。在操作过程中,采用深低温停循环(DHCA)和右腋窝动脉选择性顺行脑灌注(ACP)进行脑保护。进行了“包含”全主动脉弓置换和支架象鼻(SET)手术。
    结果:研究期间有4名患者接受了Bentall手术,另外一名患者由于右冠孔严重受累而需要冠状动脉旁路移植术(CABG)。3例患者在术后住院期间死亡。其他值得注意的并发症包括2例术后肾功能衰竭,需要连续肾脏替代疗法(CRRT)。术后双下肢截瘫1例,1例脑梗塞导致左上肢单侧损伤。术后三个月至一年,对11例患者进行了主动脉计算机断层扫描血管造影(CTA)检查。CTA结果显示7例患者主动脉弓支架周围的假腔血栓形成,8例患者降主动脉支架周围的假腔完全血栓形成。一名患者在降主动脉支架周围的假腔部分血栓形成,随访一年后,另一名患者的胸主动脉和腹主动脉假腔完全消退。
    结论:在主动脉弓置换中合并血管移植物可简化手术并产生有希望的短期结果。它使用四分支假体移植物实现了全足弓置换的目的。然而,广泛的采样和彻底的,长期随访观察对于全面评估长期结果至关重要.
    BACKGROUND: This study aimed to elucidate the methodology and assess the efficacy of the aortic arch inclusion technique using an artificial blood vessel in managing acute type A aortic dissection (ATAAD).
    METHODS: We conducted a retrospective review of 18 patients (11 males and 7 females, average age: 56.2 ± 8.6 years) diagnosed with ATAAD who underwent total aortic arch replacement (TAAR) using an artificial vascular \"inclusion\" between June 2020 and October 2022. During the operation, deep hypothermic circulatory arrest (DHCA) and selective antegrade cerebral perfusion (ACP) of the right axillary artery were employed for brain protection. The \'inclusion\' total aortic arch replacement and stented elephant trunk (SET) surgery were performed.
    RESULTS: Four patients underwent the Bentall procedure during the study, with one additional patient requiring coronary artery bypass grafting (CABG) due to significant involvement of the right coronary orifice. Three patients died during postoperative hospitalization. Other notable complications included two cases of postoperative renal failure necessitating continuous renal replacement therapy (CRRT), one case of postoperative double lower limb paraplegia, and one case of cerebral infarction resulting in unilateral impairment of the left upper limb. Eleven patients underwent computed tomography angiography (CTA) examinations of the aorta three months to one-year post-operation. The CTA results revealed thrombosis in the false lumen surrounding the aortic arch stent in seven patients and complete thrombosis of the false lumen around the descending aortic stent in eight patients. One patient had partial thrombosis of the false lumen around the descending aortic stent, and another patient\'s false lumen in the thoracic and abdominal aorta completely resolved after one year of follow-up.
    CONCLUSIONS: Incorporating vascular graft in aortic arch replacement simplifies the procedure and yields promising short-term outcomes. It achieves the aim of total arch replacement using a four-branch prosthetic graft. However, extensive sampling and thorough, prolonged follow-up observations are essential to fully evaluate the long-term results.
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  • 文章类型: Journal Article
    微流体技术已经成为研究动脉血栓形成的强大工具,允许研究人员构建人造血管并复制血流的血液动力学。该技术在理解血栓形成和血小板粘附和聚集方面取得了重大进展。微流体模型具有各种类型和功能,通过研究微流控芯片的制作方法和工作原理,可根据具体需要选择适用的方法。微流控集成系统和模块化微流控系统的快速发展使得动脉血栓研究更加多样化和自动化,但其标准化仍亟待解决。微流体技术的一个关键优势是能够精确控制微通道中的流体流动并分析在不同剪切力和流速下的血小板行为。这使研究人员能够研究血液流动的生理和病理过程,阐明动脉血栓形成的潜在机制。总之,微流控技术通过构建人造血管和准确再现血液动力学,彻底改变了动脉血栓形成的研究。在未来,微流体将更加重视多功能性和自动化,在推进抗血栓治疗和预防措施方面大有希望。
    背景是什么?为了研究动脉血栓形成的机制,包括血小板粘附和聚集行为以及凝血过程。微流体技术通常用于研究血栓形成。微流控技术可以在体外微观尺度上模拟真实的生理环境,具有高吞吐量,低成本,和快速的速度。作为一个创新的实验平台,微流控技术已经取得了显著的进步,并在生物和医学领域得到了应用。本文综述了微流体的不同制造方法,并比较了这些方法的优缺点。微流体集成系统和模块化微流体系统的最新发展已导致未来更多样化和自动化的微流体芯片。总结了微流控模型的不同类型和功能。血小板粘附聚集和凝血过程,以及动脉血栓相关的剪切力变化和力学行为,通过构建人工血管和再现血流动力学进行了研究。微流控技术可为制定个性化血栓治疗策略提供依据。通过分析现有药物的作用机制,使用微流控技术进行药物的高通量筛选和药物疗效评估,可以开发更多的药物治疗可能性。有什么影响?这篇综述利用微流体技术进一步推进动脉血栓形成的研究,微流体也有望在未来的生物医学领域发挥更大的作用。
    Microfluidic technology has emerged as a powerful tool in studying arterial thrombosis, allowing researchers to construct artificial blood vessels and replicate the hemodynamics of blood flow. This technology has led to significant advancements in understanding thrombosis and platelet adhesion and aggregation. Microfluidic models have various types and functions, and by studying the fabrication methods and working principles of microfluidic chips, applicable methods can be selected according to specific needs. The rapid development of microfluidic integrated system and modular microfluidic system makes arterial thrombosis research more diversified and automated, but its standardization still needs to be solved urgently. One key advantage of microfluidic technology is the ability to precisely control fluid flow in microchannels and to analyze platelet behavior under different shear forces and flow rates. This allows researchers to study the physiological and pathological processes of blood flow, shedding light on the underlying mechanisms of arterial thrombosis. In conclusion, microfluidic technology has revolutionized the study of arterial thrombosis by enabling the construction of artificial blood vessels and accurately reproducing hemodynamics. In the future, microfluidics will place greater emphasis on versatility and automation, holding great promise for advancing antithrombotic therapeutic and prophylactic measures.
    What is the context? To study the mechanism of arterial thrombosis, including the platelet adhesion and aggregation behavior and the coagulation process.Microfluidic technology is commonly used to study thrombosis. Microfluidic technology can simulate the real physiological environment on the microscopic scale in vitro, with high throughput, low cost, and fast speed.As an innovative experimental platform, microfluidic technology has made remarkable progress and has found applications in the fields of biology and medicine.What is new? This review summarizes the different fabrication methods of microfluidics and compares the advantages and disadvantages of these methods. Recent developments in microfluidic integrated systems and modular microfluidic systems have led to more diversified and automated microfluidic chips in the future.The different types and functions of microfluidic models are summarized. Platelet adhesion aggregation and coagulation processes, as well as arterial thrombus-related shear force changes and mechanical behaviors, were investigated by constructing artificial blood vessels and reproducing hemodynamics.Microfluidics can provide a basis for the development of personalized thrombosis treatment strategies. By analyzing the mechanism of action of existing drugs, using microfluidic technology for high-throughput screening of drugs and evaluating drug efficacy, more drug therapy possibilities can be developed.What is the impact?This review utilizes microfluidics to further advance the study of arterial thrombosis, and microfluidics is also expected to play a greater role in the biomedical field in the future.
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  • 文章类型: Journal Article
    血管是血液流经的管道,分为三种类型:毫米级的动脉,静脉,和毛细血管以及微米尺度的毛细血管。动脉和静脉是输送血液的管道,而毛细血管是血液与组织交换物质的地方。血管主要由胶原纤维组成,弹性纤维,糖胺聚糖和其他大分子物质。人体每平方英寸的皮肤大约有19英尺的血管,这显示了血管对人体的重要性。因为心血管疾病和血管创伤在人群中很常见,近年来进行了大量的研究,通过模拟人体自身血管的结构和功能,创造出不同水平的组织工程血管,可以替代人体内受损的血管。然而,由于缺乏有效的氧气和营养输送机制,这些组织工程血管尚未在临床上使用。因此,为了更好地实现工程化血管组织的血管化,研究人员已经广泛探索了各种尺寸的血管系统的设计方法。在不久的将来,这些精心设计和构建的组织工程血管有望在临床上有实际应用。探索如何形成多尺度血管网络并提高其与宿主血管系统的兼容性将非常有利于实现这一目标。其中,3D打印具有精度高、设计灵活等优点,去细胞化的基质保留了胶原蛋白等活性成分,弹性蛋白,和糖胺聚糖,同时去除免疫原性物质DNA。在这次审查中,系统讨论了3D打印和基于脱细胞的人造血管制造方法的技术和进展。详细介绍了最近设计的血管系统的示例,讨论并指出了血管组织限制临床应用中存在的主要问题和挑战,并对组织工程血管领域未来的发展趋势进行了展望。
    Blood vessels are the tubes through which blood flows and are divided into three types: millimeter-scale arteries, veins, and capillaries as well as micrometer-scale capillaries. Arteries and veins are the conduits that carry blood, while capillaries are where blood exchanges substances with tissues. Blood vessels are mainly composed of collagen fibers, elastic fibers, glycosaminoglycans and other macromolecular substances. There are about 19 feet of blood vessels per square inch of skin in the human body, which shows how important blood vessels are to the human body. Because cardiovascular disease and vascular trauma are common in the population, a great number of researches have been carried out in recent years by simulating the structures and functions of the person\'s own blood vessels to create different levels of tissue-engineered blood vessels that can replace damaged blood vessels in the human body. However, due to the lack of effective oxygen and nutrient delivery mechanisms, these tissue-engineered vessels have not been used clinically. Therefore, in order to achieve better vascularization of engineered vascular tissue, researchers have widely explored the design methods of vascular systems of various sizes. In the near future, these carefully designed and constructed tissue engineered blood vessels are expected to have practical clinical applications. Exploring how to form multi-scale vascular networks and improve their compatibility with the host vascular system will be very beneficial in achieving this goal. Among them, 3D printing has the advantages of high precision and design flexibility, and the decellularized matrix retains active ingredients such as collagen, elastin, and glycosaminoglycan, while removing the immunogenic substance DNA. In this review, technologies and advances in 3D printing and decellularization-based artificial blood vessel manufacturing methods are systematically discussed. Recent examples of vascular systems designed are introduced in details, the main problems and challenges in the clinical application of vascular tissue restriction are discussed and pointed out, and the future development trends in the field of tissue engineered blood vessels are also prospected.
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  • 文章类型: Journal Article
    能够在流体浸没环境中有效执行任务的软机器人在各种应用中具有广阔的前景。然而,它仍然具有挑战性,以实现机器人化,依靠动态水下粘附和变形能力。在这里,我们建议使用设计师的蛋白质材料构建此类机器人。首先,Resilin样蛋白质与多金属氧酸盐阴离子络合形成水凝胶,可在含水环境中响应小的温度变化而在软粘性和硬非粘性状态之间快速切换。为了实现动态粘附和变形的远程控制,然后将Fe3O4纳米颗粒整合到水凝胶中以形成具有光热和磁响应性的软机器人。这些机器人被证明可以承担复杂的任务,包括修复人造血管,在红外光和磁场的协同控制下,在水中捕获和交付多个货物。这些发现为创建具有按需功能的基于蛋白质的水下机器人铺平了道路。
    Soft robots capable of efficiently implementing tasks in fluid-immersed environments hold great promise for diverse applications. However, it remains challenging to achieve robotization that relies on dynamic underwater adhesion and morphing capability. Here we propose the construction of such robots with designer protein materials. Firstly, a resilin-like protein is complexed with polyoxometalate anions to form hydrogels that can rapidly switch between soft adhesive and stiff non-adhesive states in aqueous environments in response to small temperature variation. To realize remote control over dynamic adhesion and morphing, Fe3O4 nanoparticles are then integrated into the hydrogels to form soft robots with photothermal and magnetic responsiveness. These robots are demonstrated to undertake complex tasks including repairing artificial blood vessel, capturing and delivering multiple cargoes in water under cooperative control of infrared light and magnetic field. These findings pave an avenue for the creation of protein-based underwater robots with on-demand functionalities.
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  • 文章类型: Journal Article
    科学文献中报道了关于新型基于血红蛋白的氧载体(HBOC)的配方和临床应用的许多研究。然而,与HBOCs相关的科学计量分析较少。这里,我们使用科学计量分析方法和范围审查方法说明了最近对HBOCs的研究。我们利用前者调查了1991年至2022年对HBOCs的研究,探索了当前的热点和研究趋势,然后在关键词分析的基础上全面分析了概念之间的关系。研究领域的演变,知识结构,通过科学计量分析揭示了HBOCs所在的研究主题。类型的阐明,作用机制,潜在的临床实践,HBOCs的不利影响有助于阐明这种生物制剂的前景。科学计量学分析了该研究领域的1034种出版物,这些发现为进一步研究提供了有希望的路线图。
    Numerous studies on the formulation and clinical applications of novel hemoglobin-based oxygen carriers (HBOCs) are reported in the scientific literature. However, there are fewer scientometric analysis related to HBOCs. Here, we illustrate recent studies on HBOCs using both a scientometric analysis approach and a scope review method. We used the former to investigate research on HBOCs from 1991 to 2022, exploring the current hotspots and research trends, and then we comprehensively analyzed the relationship between concepts based on the keyword analysis. The evolution of research fields, knowledge structures, and research topics in which HBOCs located are revealed by scientometric analysis. The elucidation of type, acting mechanism, potential clinical practice, and adverse effects of HBOCs helps to clarify the prospects of this biological agent. Scientometrics analyzed 1034 publications in this research field, and these findings provide a promising roadmap for further study.
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  • 文章类型: Journal Article
    小直径人造血管越来越多地用于临床实践。然而,这些血管容易出现血栓,有必要改善血液相容性。表面涂覆是这方面常用的方法之一。受贻贝仿生的启发,最近,使用沉积技术在纤维表面获得涂层覆盖显著激起了研究人员的兴趣。在这项研究中,由聚(己内酯)复合材料组成的管状支架,醋酸纤维素,和单宁酸(TA)进行静电纺丝,然后用不同的Fe(III)溶液(氯化铁(III)六水合物(FeCl3\'6H2O))处理支架,获得四个管状支架:F0,F5,F15和F45。根据扫描电子显微镜(SEM)和场发射-SEM结果,后处理后将TA/Fe(III)复合物涂覆在支架的纤维上;纤维表面形貌随Fe(III)浓度的不同而变化。这为管状支架的性能提供了可设计性。F5管状支架的抗拉强度(3.33MPa)高于F45(3.14MPa),而F45管状支架的应变(83.9%)是F5(37.2%)的2.26倍。此外,评估了细胞毒性和抗血栓形成性能。试验结果表明,表面TA/Fe(III)涂层处理可影响支架表面的细胞毒性和抗凝性能。本研究中使用的贻贝仿生TA/Fe(III)涂层改善了人造血管的性能。
    Small-diameter artificial blood vessels are increasingly being used in clinical practice. However, these vessels are prone to thrombus, and it is necessary to improve blood compatibility. Surface coating is one of the commonly used methods in this regard. Inspired by the biomimicry of mussels, the use of deposition technology to obtain coating coverage on the surface of fibers has significantly piqued the interest of researchers recently. In this study, tubular scaffolds consisting of a composite of poly(caprolactone), cellulose acetate, and tannic acid (TA) were electrospun, and then the scaffolds were treated with different Fe(III) solutions (iron(III) chloride hexahydrate (FeCl3\'6H2O)) to obtain four tubular scaffolds: F0, F5, F15, and F45. According to scanning electron microscopy (SEM) and field emission-SEM results, TA/Fe(III) complex is coated on the fiber of the scaffold after post-treatment; the fiber surface morphology changes with different Fe(III) concentrations. This provides designability to the performance of tubular scaffolds. The tensile strength of the F5 tubular scaffold (3.33 MPa) is higher than that of F45 (3.14 MPa), while the strain (83.9%) of the F45 tubular stent was 2.26 times that of the F5 (37.2%). In addition, cytotoxicity and antithrombotic performance were evaluated. The test results show that surface TA/Fe(III) coating treatment can affect the cytotoxicity and anticoagulation performance of the scaffold surface. The biomimetic TA/Fe(III) coating of mussels used in this study improves the performance of artificial blood vessels.
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  • 文章类型: Journal Article
    缺血或缺氧可导致组织代谢和功能的病理变化,进而导致各种疾病。及时有效的血液复苏或改善缺氧对疾病的治疗非常重要。然而,有必要发展稳定,无毒,以及由于血液短缺等限制而导致的免疫惰性氧载体,不同的血型,以及传播感染的风险。随着各种技术的发展,近年来,基于血红蛋白和全氟化碳的氧载体得到了广泛的研究。本文综述了血红蛋白和全氟化碳氧载体的发展和应用。分析了氧载体的设计,讨论了它们在各种低氧疾病中作为血液替代品或氧载体的应用。最后,对理想载氧材料的特点及未来研究进行了展望,以期为后续研究提供参考。
    Ischemia or hypoxia can lead to pathological changes in the metabolism and function of tissues and then lead to various diseases. Timely and effective blood resuscitation or improvement of hypoxia is very important for the treatment of diseases. However, there is a need to develop stable, nontoxic, and immunologically inert oxygen carriers due to limitations such as blood shortages, different blood types, and the risk of transmitting infections. With the development of various technologies, oxygen carriers based on hemoglobin and perfluorocarbon have been widely studied in recent years. This paper reviews the development and application of hemoglobin and perfluorocarbon oxygen carriers. The design of oxygen carriers was analyzed, and their application as blood substitutes or oxygen carriers in various hypoxic diseases was discussed. Finally, the characteristics and future research of ideal oxygen carriers were prospected to provide reference for follow-up research.
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  • 文章类型: Journal Article
    人造血管和宿主血管之间的顺应性不匹配导致异常的血液动力学,并且是内膜增生的主要机械触发因素。已经努力实现人造血管的更高顺应性。然而,尚未实现与宿主血管顺应性匹配的人造血管的制备。使用聚(L-丙交酯-共聚-己内酯)(PLCL)和热塑性聚(醚氨基甲酸酯)(TPU),通过浸涂和静电纺丝复合方法成功制备了双层人造血管。在一定壁厚(200μm)的情况下,PLCL内层(浸涂法)和TPU外层(静电纺丝法)的厚度比分别控制在0:1、1:9、3:7、5:5、7:3和1:0,径向拉伸性能,爆破压力,和缝合线保留强度进行了研究。结果表明,人工血管的顺应性值随着厚度比的增加而降低,这表明可以通过调节内层和外层厚度的比率来调节双层人造血管的顺应性。在六种不同的人造血管中,厚度比为1:9的材料不仅具有较高的顺应性(8.768±0.393%/100mmHg),而且可以保证其他机械性能,如径向断裂强度(6.333±0.689N/mm),爆破压力(534.473±20.899mmHg),和缝合线保留强度(300.773±9.351cN)。所提出的人工血管制备方法有望实现与宿主血管的顺应性匹配。它有利于消除异常的血流动力学和减少内膜增生。
    Compliance mismatch between the artificial blood vessel and the host vessel leads to abnormal hemodynamics and is a major mechanical trigger of intimal hyperplasia. Efforts have been made to achieve higher compliance of artificial blood vessels. However, the preparation of artificial blood vessels with compliance matching to host vessels has not been realized. A bi-layered artificial blood vessel was successfully prepared by dip-coating and electrospinning composite method using poly(L-Lactide-co-caprolactone) (PLCL) and thermoplastic poly(ether urethane) (TPU). In the case of a certain wall thickness (200 μm), thickness ratios of the PLCL inner layer (dip-coating method) and TPU outer layer (electrospinning method) were controlled at 0:1, 1:9, 3:7, 5:5, 7:3, and 1:0 respectively and the compliance, radial tensile properties, burst pressure, and suture retention strength were investigated. Results showed compliance value of the artificial blood vessel decreased with the increase of the thickness ratio, which suggested the compliance of the bi-layered artificial blood vessel can be regulated by adjusting the ratio of the inner and outer layer thicknesses. In the six different artificial blood vessels, the one with thickness ratio of 1:9 not only had high compliance (8.768 ± 0.393%/100 mmHg) but also can guarantee the other mechanical properties, such as the radial breaking strength (6.333 ± 0.689 N/mm), burst pressure (534.473 ± 20.899 mmHg), and suture retention strength (300.773 ± 9.351 cN). The proposed artificial blood vessel preparation method is expected to achieve compliance matching with the host vessel. It is beneficial for eliminating abnormal hemodynamics and reducing intimal hyperplasia.
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  • 文章类型: Journal Article
    基于血红蛋白的氧载体(HBOC)的开发是院前紧急输血的极好补充。在这项研究中,通过使用人脐带血红蛋白(HCHb)和戊二醛(GDA)和双(3,5-二溴水杨酸)富马酸(DBBF)修饰(DBBF-GDA-HCHb)制备了一种新型的HBOC,评价了其制备过程中理化指标的变化,虽然准备了传统类型的GDA-HCHb,并通过135.0%交换输血(ET)的大鼠模型评估了两种HBOC的携氧能力。选择18只SD雄性大鼠,并随机分为对照组(5.0%白蛋白),DBBF-GDA-HCHb组和GDA-HCHb组。C组12h生存率为16.67%,两个HBOC组均为83.33%。与GDA-HCHb相比,DBBF-GDA-HCHb可以通过更及时地为缺氧组织提供氧气来降低乳酸含量,还可以改善因缺血引起的MAP降低。
    The development of haemoglobin-based oxygen carrier (HBOC) is an excellent supplement to pre-hospital emergency blood transfusions. In this study, a new type of HBOC was prepared by using human cord haemoglobin (HCHb) and glutaraldehyde (GDA) and Bis(3,5-dibromosalicyl) fumarate (DBBF) to modify (DBBF-GDA-HCHb), the changes of physicochemical indexes during its preparation were evaluated, while a traditional type of GDA-HCHb was prepared, and the oxygen-carrying capacity of two type of HBOC was evaluated by a rat model of 135.0% exchange transfusion (ET). Eighteen SD male rats were selected, and were randomly divided into control group (5.0% albumin), DBBF-GDA-HCHb group and GDA-HCHb group. The 12 h survival rate of the C group was 16.67%, and the two HBOC groups were both 83.33%. Compared with GDA-HCHb, DBBF-GDA-HCHb can reduce lactic acid content by supplying oxygen to hypoxic tissues in a more timely manner, and can also can improve the reduction of MAP due to ischaemia.
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