RESUMO
BACKGROUND: A 54-year-old Hispanic OPos female with known history of anti-Rh17 antibodies was diagnosed with Philadelphia-Chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Rh17, also known as Hr0, is a high-frequency antigen composed of several epitopes on the RhCE protein. Anti-Rh17 antibodies can be made by individuals with missing or varied C/c, E/e antigens. Anti-Rh17 antibodies are clinically significant given multiple case reports of hemolytic disease of the fetus and newborn (HDFN). Finding compatible units for patients with anti-Rh17 can be particularly difficult given that only 1 in 100,000 people are Rh17 negative. STUDY DESIGN AND METHODS: Search for compatible units was conducted by the American Rare Donor Program (ARDP) with no leads. After chemotherapy induction and despite erythropoiesis stimulating agent administration, the patient's hemoglobin continued to trend down to a nadir of 2.8 g/dL. Here we report transfusion of incompatible pRBC to this patient with critically symptomatic anemia. HBOC-201 (Hemopure) was obtained and administered under an emergency compassionate/expanded access designation from the Food and Drug Administration (FDA) under an emergency Investigational New Drug (IND) application. RESULTS AND DISCUSSION: Overall difficulties in this case included the challenge of finding compatible units, dilemma of transfusing incompatible units in a patient with severe anemia and obtaining alternatives to blood products. This case report demonstrates the successful use of HBOC-21 in treating life-threatening anemia.
Assuntos
Hemoglobinas , Humanos , Feminino , Pessoa de Meia-Idade , Isoanticorpos/imunologia , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Substitutos Sanguíneos/uso terapêutico , Transfusão de EritrócitosRESUMO
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.
Assuntos
Substitutos Sanguíneos , Trombose , Humanos , Microfluídica/métodos , Plaquetas/patologia , Trombose/patologia , Adesividade PlaquetáriaRESUMO
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.
Assuntos
Substitutos Sanguíneos , Hemoglobinas , Lipossomos , Nanoestruturas , Oxigênio , Humanos , Hemoglobinas/química , Hemoglobinas/metabolismo , Substitutos Sanguíneos/química , Oxigênio/química , Animais , Nanoestruturas/química , Lipossomos/química , Nanocápsulas/química , Cicatrização/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Choque Hemorrágico/tratamento farmacológicoRESUMO
The review presents the results of the blood substitute development based on perfluororganic compounds (PFC). The limitations of PFC due to which their further development was suspended are described. The presented data allows us to imagine a possible way to create optimal drugs based on PFC. Chemically inactive perfluorocomponents should be used - perfluorinated hydrocarbons and tertiary perfluorinated amines. However, in order to emulsify and stabilize the emulsion, other types of effective and chemically indifferent surfactants that do not interact with oxygen and other components of the drug are needed.
Assuntos
Substitutos Sanguíneos , Fluorocarbonos , Fluorocarbonos/química , Humanos , Tensoativos/química , Tensoativos/farmacologia , Emulsões/química , Oxigênio/química , AnimaisRESUMO
Formation of a pseudoaneurysm due to blood leakage from the anastomotic site of the vascular graft in large-diameter vessels is often seen, but formation of a pseudoaneurysm from the non-anastomotic site is extremely rare. A 68-year-old woman presented with a history of double valve replacement for combined valvular disease at 37 years old and hemiarch replacement for thoracic aortic dilatation at 65 years old. She visited the emergency room with a 2-week history of chest pain. Contrast-enhanced computed tomography (CT) revealed a 5-cm-diameter pseudoaneurysm and extravasation from the ascending aorta, so emergency surgery was performed. Around the ascending aorta area, we confirmed bleeding from a 5-mm dehiscence in the non-anastomotic part of the graft prosthesis, so hemostasis was performed with a cross-stitch mattress suture over a felt strip. Initially, the cause of the pseudoaneurysm was unknown, but re-examination of CT images from after the previous hemiarch replacement confirmed contact between the sternal wire and graft prosthesis. The wire was thus considered to have caused damage and bleeding. The patient was discharged from the hospital with a good postoperative course and is being followed-up in the outpatient department.
Assuntos
Falso Aneurisma , Implante de Prótese Vascular , Idoso , Feminino , Humanos , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/cirurgia , Aorta/cirurgia , Substitutos Sanguíneos , Implante de Prótese Vascular/efeitos adversosRESUMO
The article is devoted to historiography of perfluorocarbons, as well as discoverers of perftorane and their discoveries. There would be no national priority in transfusiology without these discoveries. Perftorane is the only one of the world series of perfluorocarbon emulsion drugs that has passed all phases of clinical trials. Perftorane has been used in clinical medicine for 30 years.
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Substitutos Sanguíneos , Fluorocarbonos , Humanos , Substitutos Sanguíneos/uso terapêutico , Fluorocarbonos/uso terapêuticoRESUMO
Is mimicking the cells that carry hemoglobin the key to a blood substitute?
Assuntos
Substitutos Sanguíneos , Hemoglobinas , Humanos , Eritrócitos , AnimaisRESUMO
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.
Assuntos
Substitutos Sanguíneos , Humanos , Substitutos Sanguíneos/análise , Engenharia Tecidual/métodos , Matriz Extracelular/química , Colágeno , Impressão Tridimensional , Alicerces TeciduaisRESUMO
Numerous scientific and medical domains have been revolutionized by nanotechnology, opening up unprecedented opportunities for healthcare applications. Among these developments, the creation of nanorobots for artificial blood components is a novel field of research that seeks to overcome the constraints of conventional pharmacological therapy. This review article provides a comprehensive overview of the nanorobotic artificial blood components and their therapeutic uses. The article begins by outlining the core concepts of nanotechnology and nanorobotic systems, emphasizing their design and control methods. It then delves into various types of nanorobotic artificial blood components, such as oxygen transporters (artificial RBCs), clotting agents (artificial platelets), and immune modulators (artificial WBCs). It goes into detail about their properties, functioning, and capabilities, which allow them to replicate the physiological activities of actual blood components. The article also assesses the clinical uses of artificial blood components in a variety of medical circumstances. It highlights their potential value in the management of certain blood-related diseases.
Assuntos
Substitutos Sanguíneos , Nanotecnologia , Humanos , Nanotecnologia/métodos , Substitutos Sanguíneos/uso terapêutico , Robótica , Plaquetas/fisiologia , EritrócitosRESUMO
ABSTRACT: Hemorrhagic shock is a major source of morbidity and mortality worldwide. While whole blood or blood product transfusion is a first-line treatment, maintaining robust supplies presents significant logistical challenges, particularly in austere environments. OMX is a novel nonhemoglobin (Hb)-based oxygen carrier derived from the H-NOX (heme-nitric oxide/oxygen binding) protein family. Because of their engineered oxygen (O 2 ) affinities, OMX proteins only deliver O 2 to severely hypoxic tissues. Additionally, unlike Hb-based oxygen carriers, OMX proteins do not scavenge nitric oxide in the vasculature. To determine the safety and efficacy of OMX in supporting tissue oxygen delivery and cardiovascular function in a large animal model of controlled hemorrhage, 2-3-week-old lambs were anesthetized, intubated, and mechanically ventilated. Hypovolemic shock was induced by acute hemorrhage to obtain a 50% reduction over 30 min. Vehicle (n = 16) or 400 mg/kg OMX (n = 13) treatment was administered over 15 min. Hemodynamics, arterial blood gases, and laboratory values were monitored throughout the 6-h study. Comparisons between groups were made using t tests, Wilcoxon rank sum test, and Fisher's exact test. Survival was assessed using Kaplan-Meier curves and the log-rank test. We found that OMX was well-tolerated and significantly improved lactate and base deficit trends, and hemodynamic indices ( P < 0.05). Median survival time was greater in the OMX-treated group (4.7 vs. 6.0 h, P < 0.003), and overall survival was significantly increased in the OMX-treated group (25% vs. 85%, P = 0.004). We conclude that OMX is well-tolerated and improves metabolic, hemodynamic, and survival outcomes in an ovine model of controlled hemorrhagic shock.
Assuntos
Modelos Animais de Doenças , Oxigênio , Choque Hemorrágico , Animais , Choque Hemorrágico/terapia , Ovinos , Hemodinâmica , Substitutos Sanguíneos/uso terapêutico , Substitutos Sanguíneos/farmacologiaRESUMO
Ticks, ectoparasitic arachnids, are prominent disease vectors impacting both humans and animals. Their unique blood-feeding phase involves significant abdominal cuticle expansion, sharing certain similarities with insects. However, vital aspects, including the mechanisms of cuticle expansion, changes in cuticular protein composition, chitin synthesis, and cuticle function, remain poorly understood. Given that the cuticle expansion is crucial for complete engorgement of the ticks, addressing these knowledge gaps is essential. Traditional tick research involving live animal hosts has inherent limitations, such as ethical concerns and host response variability. Artificial membrane feeding systems provide an alternative approach, offering controlled experimental conditions and reduced ethical dilemmas. These systems enable precise monitoring of tick attachment, feeding parameters, and pathogen acquisition. Despite the existence of various methodologies for artificial tick-feeding systems, there is a pressing need to enhance their reproducibility and effectiveness. In this context, we introduce an improved tick-feeding system that incorporates adjustments related to factors like humidity, temperature, and blood-feeding duration. These refinements markedly boost tick engorgement rates, presenting a valuable tool for in-depth investigations into tick cuticle biology and facilitating studies on molting. This refined system allows for collecting feeding ticks at specific stages, supporting research on tick cuticle biology, and evaluating chemical agents' efficacy in the engorgement process.
Assuntos
Substitutos Sanguíneos , Ixodes , Humanos , Animais , Reprodutibilidade dos Testes , BiologiaRESUMO
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.
Assuntos
Substitutos Sanguíneos , Robótica , Humanos , Fenômenos Físicos , Hidrogéis , Raios Infravermelhos , Aderências Teciduais , ÁguaRESUMO
BACKGROUND: Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available. METHODS: Purpose-bred adult dogs (n = 6) were anesthetized, instrumented, and subjected to hemorrhagic shock (mean arterial pressure <50 mm Hg or 40% blood volume loss). Then each dog was resuscitated with one of five resuscitation products: (1) lactated ringers solution and hetastarch (LRS/Heta), (2) canine chilled whole blood (CWB), (3) fresh frozen plasma (FFP) and packed red blood cells (pRBC), (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC), or (5) HBOC/FDP and canine lyophilized platelets (LyoPLT). Each dog was allowed to recover after the hemorrhage resuscitation event and was then subjected to another hemorrhage event and resuscitated with a different product until each dog was resuscitated with each product. RESULTS: At the time when animals were determined to be out of shock as defined by a shock index <1, mean arterial pressure (mmHg) values (mean ± standard error) were higher for FFP/pRBC (n = 5, 83.7 ± 4.5) and FDP/HBOC+LyoPLT (n = 4, 87.8 ± 2.1) as compared with WB (n = 4, 66.0 ± 13.1). A transient increase in creatinine was seen in dogs resuscitated with HBOC and FDP. Albumin and base excess increased in dogs resuscitated with HBOC and FDP products compared with LRS/heta and CWB ( p < 0.01). CONCLUSION: Combinations of shelf-stable blood products compared favorably to canine CWB for resolution of shock. Further research is needed to ascertain the reliability and efficacy of these shelf-stable combinations of products in other models of hemorrhage that include a component of tissue damage as well as naturally occurring trauma.
Assuntos
Modelos Animais de Doenças , Ressuscitação , Choque Hemorrágico , Animais , Cães , Choque Hemorrágico/terapia , Ressuscitação/métodos , Plasma , Substitutos Sanguíneos , Derivados de Hidroxietil Amido/administração & dosagemRESUMO
Alpha-alpha diaspirin-crosslinked human hemoglobin (DCLHb or ααHb) was a promising early generation red blood cell (RBC) substitute. The DCLHb was developed through a collaborative effort between the United States Army and Baxter Healthcare. The core design feature underlying its development was chemical stabilization of the tetrameric structure of hemoglobin (Hb) to prevent Hb intravascular dimerization and extravasation. DCLHb was developed to resuscitate warfighters on the battlefield, who suffered from life-threatening blood loss. However, extensive research revealed toxic side effects associated with the use of DCLHb that contributed to high mortality rates in clinical trials. This study explores whether scavenging Hb and heme via the apohemoglobin-haptoglobin (apoHb-Hp) complex can reduce DCLHb associated toxicity. Awake Golden Syrian hamsters were equipped with a window chamber model to characterize the microcirculation. Each group was first infused with either Lactated Ringer's or apoHb-Hp followed by a hypovolemic infusion of 10% of the animal's blood volume of DCLHb. Our results indicated that animals pretreated with apoHb-Hb exhibited improved microhemodynamics vs the group pretreated with Lactated Ringer's. While systemic acute inflammation was observed regardless of the treatment group, apoHb-Hp pretreatment lessened those effects with a marked reduction in IL-6 levels in the heart and kidneys compared to the control group. Taken together, this study demonstrated that utilizing a Hb and heme scavenger protein complex significantly reduces the microvasculature effects of ααHb, paving the way for improved HBOC formulations. Future apoHb-Hp dose optimization studies may identify a dose that can completely neutralize DCLHb toxicity.
Assuntos
Haptoglobinas , Hemoglobinas , Animais , Hemoglobinas/farmacologia , Hemoglobinas/metabolismo , Humanos , Haptoglobinas/metabolismo , Masculino , Mesocricetus , Apoproteínas/química , Apoproteínas/farmacologia , Substitutos Sanguíneos/farmacologia , Substitutos Sanguíneos/química , Reagentes de Ligações Cruzadas/química , CricetinaeRESUMO
Normothermic ex vivo lung perfusion (EVLP) can resuscitate marginal lung allografts to increase organs available for transplantation. During normothermic perfusion, cellular metabolism is more active compared with subnormothermic perfusion, creating a need for an oxygen (O 2 ) carrier in the perfusate. As an O 2 carrier, red blood cells (RBCs) are a scarce resource and are susceptible to hemolysis in perfusion circuits, thus releasing cell-free hemoglobin (Hb), which can extravasate into the tissue space, thus promoting scavenging of nitric oxide (NO) and oxidative tissue damage. Fortunately, polymerized human Hb (PolyhHb) represents a synthetic O 2 carrier with a larger molecular diameter compared with Hb, preventing extravasation, and limiting adverse reactions. In this study, a next-generation PolyhHb-based perfusate was compared to both RBC and asanguinous perfusates in a rat EVLP model. During EVLP, the pulmonary arterial pressure and pulmonary vascular resistance were both significantly higher in lungs perfused with RBCs, which is consistent with RBC hemolysis. Lungs perfused with PolyhHb demonstrated greater oxygenation than those perfused with RBCs. Post-EVLP analysis revealed that the PolyhHb perfusate elicited less cellular damage, extravasation, iron tissue deposition, and edema than either RBCs or colloid control. These results show promise for a next-generation PolyhHb to maintain lung function throughout EVLP.
Assuntos
Substitutos Sanguíneos , Hemoglobinas , Transplante de Pulmão , Perfusão , Ratos Sprague-Dawley , Hemoglobinas/administração & dosagem , Animais , Transplante de Pulmão/métodos , Transplante de Pulmão/efeitos adversos , Ratos , Perfusão/métodos , Humanos , Substitutos Sanguíneos/farmacologia , Masculino , Pulmão , Oxigênio/metabolismo , Aloenxertos , Hemólise/efeitos dos fármacos , EritrócitosRESUMO
Lung transplantation is hampered by the lack of suitable donors. Previously, donors that were thought to be marginal or inadequate were discarded. However, new and exciting technology, such as ex vivo lung perfusion (EVLP), offers lung transplant providers extended assessment for marginal donor allografts. This dynamic assessment platform has led to an increase in lung transplantation and has allowed providers to use donors that were previously discarded, thus expanding the donor pool. Current perfusion techniques use cellular or acellular perfusates, and both have distinct advantages and disadvantages. Perfusion composition is critical to maintaining a homeostatic environment, providing adequate metabolic support, decreasing inflammation and cellular death, and ultimately improving organ function. Perfusion solutions must contain sufficient protein concentration to maintain appropriate oncotic pressure. However, current perfusion solutions often lead to fluid extravasation through the pulmonary endothelium, resulting in inadvertent pulmonary edema and damage. Thus, it is necessary to develop novel perfusion solutions that prevent excessive damage while maintaining proper cellular homeostasis. Here, we describe the application of a polymerized human hemoglobin (PolyhHb)-based oxygen carrier as a perfusate and the protocol in which this perfusion solution can be tested in a model of rat EVLP. The goal of this study is to provide the lung transplant community with key information in designing and developing novel perfusion solutions, as well as the proper protocols to test them in clinically relevant translational transplant models.
Assuntos
Hemoglobinas , Transplante de Pulmão , Pulmão , Perfusão , Animais , Ratos , Transplante de Pulmão/métodos , Hemoglobinas/química , Perfusão/métodos , Pulmão/metabolismo , Humanos , Oxigênio/metabolismo , Substitutos Sanguíneos/farmacologia , Substitutos Sanguíneos/química , Masculino , Soluções para Preservação de Órgãos/químicaRESUMO
The widespread adoption of high-calorie, high-fat, high-sucrose diets (HFHSD) has become a global health concern, particularly due to their association with cardiovascular diseases and metabolic disorders. These comorbidities increase susceptibility to severe outcomes from viral infections and trauma, with trauma-related incidents significantly contributing to global mortality rates. This context underscores the critical need for a reliable blood supply. Recent research has focused on high molecular weight (MW) polymerized human hemoglobin (PolyhHb) as a promising alternative to red blood cells (RBCs), showing encouraging outcomes in previous studies. Given the overlap of metabolic disorders and trauma-related health issues, it is crucial to assess the potential toxicity of PolyhHb transfusions, particularly in models that represent these vulnerable populations. This study evaluated the effects of PolyhHb exchange transfusion in guinea pigs that had developed metabolic disorders due to a 12-week HFHSD regimen. The guinea pigs, underwent a 20â¯% blood volume exchange transfusion with either PolyhHb or the lower molecular weight polymerized bovine hemoglobin, Oxyglobin. Results revealed that both PolyhHb and Oxyglobin transfusions led to liver damage, with a more pronounced effect observed in HFHSD-fed animals. Additionally, markers of cardiac dysfunction indicated signs of cardiac injury in both the HFHSD and normal diet groups following the Oxyglobin transfusion. This study highlights how pre-existing metabolic disorders can exacerbate the potential side effects of hemoglobin-based oxygen carriers (HBOCs). Importantly, the newer generation of high MW PolyhHb showed lower cardiac toxicity compared to the earlier generation low MW PolyhHb, known as Oxyglobin, even in models with pre-existing endothelial and metabolic challenges.
Assuntos
Doenças Cardiovasculares , Hemoglobinas , Doenças Metabólicas , Peso Molecular , Animais , Hemoglobinas/metabolismo , Hemoglobinas/farmacologia , Cobaias , Masculino , Modelos Animais de Doenças , Dieta Hiperlipídica/efeitos adversos , Humanos , Substitutos Sanguíneos/farmacologiaRESUMO
Haemorrhagic shock is a leading cause of death worldwide. Blood transfusions can be used to treat patients suffering severe blood loss but donated red blood cells (RBCs) have several limitations that limit their availability and use. To solve the problems associated with donated RBCs, several acellular haemoglobin-based oxygen carriers (HBOCs) have been developed to restore the most important function of blood: oxygen transport. One promising HBOC is the naturally extracellular haemoglobin (i.e. erythrocruorin) of Lumbricus terrestris (LtEc). The goal of this study was to maximise the portability of LtEc by lyophilising it and then testing its stability at elevated temperatures. To prevent oxidation, several cryoprotectants were screened to determine the optimum formulation for lyophilisation that could minimise oxidation of the haem iron and maximise recovery. Furthermore, samples were also deoxygenated prior to storage to decrease auto-oxidation, while resuspension in a solution containing ascorbic acid was shown to partially reduce LtEc that had oxidised during storage (e.g. from 42% Fe3+ to 11% Fe3+). Analysis of the oxygen equilibria and size of the resuspended LtEc showed that the lyophilisation, storage, and resuspension processes did not affect the oxygen transport properties or the structure of the LtEc, even after 6 months of storage at 40 °C. Altogether, these efforts have yielded a shelf-stable LtEc powder that can be stored for long periods at high temperatures, but future animal studies will be necessary to prove that the resuspended product is a safe and effective oxygen transporter in vivo.
Assuntos
Liofilização , Hemoglobinas , Oligoquetos , Animais , Oligoquetos/metabolismo , Hemoglobinas/química , Hemoglobinas/metabolismo , Oxigênio/metabolismo , Oxigênio/química , Oxirredução , Substitutos Sanguíneos/químicaRESUMO
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.