人工血液:我们现在在哪里?

Amany A.E. Ahmed
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Immunological effects of blood transfusions are associated with a higher frequency of infectious processes during surgery, slowing of wound healing and progression of malignant diseases. Requirements for an ideal AB preparation include adequate oxygen uptake and delivery under physiological conditions, no toxic or physiological effects, ability to be eliminated and excreted by the human body, sufficient intravascular half-life, ease of use and storage, stability at room temperature, universal compatibility, availability and low cost, ability to maintain blood pressure and pH, viscosity similar to real blood. Available AOC include oxygen-transport solutions based on hemoglobin and perfluorocarbon compounds (PFC) in the form of emulsions. Natural (human, bovine) or genetically modified hemoglobin is used for the production of the former, and hemoglobin of yeast or bacterial origin can also be used. The advantages of hemoglobin solutions include the increased erythropoietin production, adequate oxygen delivery at a hemoglobin level of 20 g/L without side effects, complete absence of virus transmission and 25 % better reperfusion recovery than with real blood. Potential fields of AOC use include shock, organ ischemia, erythrocyte incompatibility, acute lung injury, organ storage for transplantation, cardioplegia, sickle cell anemia, tumor treatment, and air embolism. The main problem is the release of pro-inflammatory cytokines in response to hemoglobin solution administration. Side effects of these solutions include neuro- and nephrotoxicity, immunosuppression, vasoconstriction, coagulopathy, release of free radicals, and errors in blood tests. In turn, PFC does not bind oxygen, but dissolves it in proportion to the partial pressure. PFC are eliminated by phagocytes and eventually excreted by the lungs during respiration. PFC particles are much smaller than natural erythrocytes (0.2 vs. 7 μm) and are easier to deform, which facilitates their delivery to ischemic areas. Side effects of PFC include transient face flushing, headache and back pain, nausea, fever, anaphylactoid reactions, bleeding tendency, pulmonary edema, and acute right ventricular failure. Because high partial pressures are required to achieve the desired PFC effects, artificial lung ventilation may be required. In addition to hemoglobin-based AOC and PFC, hemoglobin in liposomal erythrocyte form, hemoglobin in nanocapsules, nanoarchitectonic complexes of hemoglobin are under development. \nConclusions. 1. The creation of AB may revolutionize medicine. 2. The need to create an AB is justified by the high cost of collection, processing and storage of donor blood, its low infectious safety, reduction of the number of donors, problems due to blood incompatibility. 3. 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引用次数: 0

摘要

背景。人工血液(AB)和/或其成分的产生可以改变药物,但目前可用的人工氧载体(AOC)不执行其他血液功能:血管容量维持、凝血、免疫、神经递质运输、营养物质和废物。目标。描述AB材料和方法的现状。对这一问题的文献资料进行分析。结果和讨论。由于采集、处理和储存献血者血液的成本较高,抗艾滋病毒、病毒性乙型和丙型肝炎、巨细胞病毒等药物的感染安全性较低,献血者数量减少,以及血液不相容的问题,因此有必要创建AB。输血的免疫效应与手术过程中感染过程的较高频率、伤口愈合的减慢和恶性疾病的进展有关。理想的AB制剂的要求包括生理条件下足够的氧气摄取和输送,无毒性或生理效应,能够被人体消除和排泄,足够的血管内半衰期,易于使用和储存,室温稳定性,通用兼容性,可用性和低成本,维持血压和pH值的能力,粘度类似于真正的血液。可用的AOC包括基于血红蛋白和全氟碳化合物(PFC)的乳剂形式的氧传输溶液。前者的生产使用天然(人、牛)或转基因血红蛋白,酵母或细菌血红蛋白也可以使用。血红蛋白溶液的优点包括红细胞生成素的产生增加,血红蛋白水平为20 g/L时的充足氧气输送,无副作用,完全没有病毒传播,再灌注恢复比真血好25%。AOC应用的潜在领域包括休克、器官缺血、红细胞不相容、急性肺损伤、器官移植储存、心脏骤停、镰状细胞性贫血、肿瘤治疗和空气栓塞。主要的问题是促炎细胞因子的释放对血红蛋白溶液的反应。这些溶液的副作用包括神经和肾毒性、免疫抑制、血管收缩、凝血功能障碍、自由基释放和血液检查错误。反过来,PFC不结合氧气,而是按分压的比例溶解氧气。PFC被吞噬细胞清除,最终在呼吸过程中由肺排出。PFC颗粒比天然红细胞小得多(0.2 μm vs. 7 μm),更容易变形,这有利于它们递送到缺血区域。PFC的副作用包括短暂的面部潮红、头痛和背痛、恶心、发烧、类过敏反应、出血倾向、肺水肿和急性右心室衰竭。由于需要较高的分压才能达到预期的PFC效果,因此可能需要人工肺通气。除了基于血红蛋白的AOC和PFC,血红蛋白脂质体红细胞形式,血红蛋白纳米胶囊,血红蛋白纳米结构复合物正在开发中。结论:1。AB的诞生可能会给医学带来革命性的变化。2. 由于献血者血液的收集、处理和储存成本高、感染安全性低、献血者数量减少以及血液不相容造成的问题,建立AB的必要性是合理的。3.AOC包括基于血红蛋白的氧转运溶液和PFC乳剂。4. 需要进一步的研究来改进现有的AB制剂,并创建新的AB制剂。
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Artificial blood: where are we now?
Background. The creation of artificial blood (AB) and/or its components can change medicine, but currently available artificial oxygen carriers (AOC) do not perform other blood functions: vascular volume maintenance, coagulation, immunity, transport of neurotransmitters, nutrients and waste. Objective. To describe the current situation regarding AB. Materials and methods. Analysis of literature data on this issue. Results and discussion. The need to create an AB is justified by the high cost of collecting, processing and storing donor blood, low infectious safety of drugs received against HIV, viral hepatitis B and C, cytomegalovirus, etc., reduction of the number of donors, problems with blood incompatibility. Immunological effects of blood transfusions are associated with a higher frequency of infectious processes during surgery, slowing of wound healing and progression of malignant diseases. Requirements for an ideal AB preparation include adequate oxygen uptake and delivery under physiological conditions, no toxic or physiological effects, ability to be eliminated and excreted by the human body, sufficient intravascular half-life, ease of use and storage, stability at room temperature, universal compatibility, availability and low cost, ability to maintain blood pressure and pH, viscosity similar to real blood. Available AOC include oxygen-transport solutions based on hemoglobin and perfluorocarbon compounds (PFC) in the form of emulsions. Natural (human, bovine) or genetically modified hemoglobin is used for the production of the former, and hemoglobin of yeast or bacterial origin can also be used. The advantages of hemoglobin solutions include the increased erythropoietin production, adequate oxygen delivery at a hemoglobin level of 20 g/L without side effects, complete absence of virus transmission and 25 % better reperfusion recovery than with real blood. Potential fields of AOC use include shock, organ ischemia, erythrocyte incompatibility, acute lung injury, organ storage for transplantation, cardioplegia, sickle cell anemia, tumor treatment, and air embolism. The main problem is the release of pro-inflammatory cytokines in response to hemoglobin solution administration. Side effects of these solutions include neuro- and nephrotoxicity, immunosuppression, vasoconstriction, coagulopathy, release of free radicals, and errors in blood tests. In turn, PFC does not bind oxygen, but dissolves it in proportion to the partial pressure. PFC are eliminated by phagocytes and eventually excreted by the lungs during respiration. PFC particles are much smaller than natural erythrocytes (0.2 vs. 7 μm) and are easier to deform, which facilitates their delivery to ischemic areas. Side effects of PFC include transient face flushing, headache and back pain, nausea, fever, anaphylactoid reactions, bleeding tendency, pulmonary edema, and acute right ventricular failure. Because high partial pressures are required to achieve the desired PFC effects, artificial lung ventilation may be required. In addition to hemoglobin-based AOC and PFC, hemoglobin in liposomal erythrocyte form, hemoglobin in nanocapsules, nanoarchitectonic complexes of hemoglobin are under development. Conclusions. 1. The creation of AB may revolutionize medicine. 2. The need to create an AB is justified by the high cost of collection, processing and storage of donor blood, its low infectious safety, reduction of the number of donors, problems due to blood incompatibility. 3. AOC include hemoglobin-based oxygen-transporting solutions and PFC emulsions. 4. Further studies are needed to improve existing AB preparations and create new ones.
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