Innate Immune Response After Resuscitation With Hemoglobin-Based Oxygen Carrier and Recombinant Factor VIIA in Uncontrolled Hemorrhagic Shock in a Swine Model

Malkevich, Nina; Dong, Feng; VanderMolen, C.; Philbin, Nora; Rice, Jennifer; Scultetus, Anke; Jiang, Hong; Arnaud, Françoise; Hall, C.; McGwin, Gerald; Pearce, L. Bruce; Handrigan, Michael; Ahlers, Stephen; McCarron, Richard M.; Freilich, Daniel

doi:10.1097/ta.0b013e3181454a05

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…Arnaud et al in a preclinical study showed that transfusion of HBOC-201 successfully resuscitated and avoided blood transfusion in animals, but it caused dilutional coagulopathy (lower hematocrit, platelets, and fibrinogen) ( 66 ). HBOC-201 combined with other coagulation substances such as freeze-dried plasma (FDP) ( 67 ) or recombinant coagulation factor VIIa (rfVIIa) that had little effect on functional coagulation indicators and had no significant survival benefit ( 68 ). However, in the combination of a bleeding model with the Folts model, due to the interaction of many factors such as platelet count, hematocrit, and platelet aggregation, HBOC-201 can reduce thrombosis ( 69 ).…”

Section: Trauma and Hemorrhagic Shockmentioning

confidence: 99%

New Applications of HBOC-201: A 25-Year Review of the Literature

Cao

Zhao

et al. 2021

Front. Med.

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If not cured promptly, tissue ischemia and hypoxia can cause serious consequences or even threaten the life of the patient. Hemoglobin-based oxygen carrier-201 (HBOC-201), bovine hemoglobin polymerized by glutaraldehyde and stored in a modified Ringer's lactic acid solution, has been investigated as a blood substitute for clinical use. HBOC-201 was approved in South Africa in 2001 to treat patients with low hemoglobin (Hb) levels when red blood cells (RBCs) are contraindicated, rejected, or unavailable. By promoting oxygen diffusion and convective oxygen delivery, HBOC-201 may act as a direct oxygen donor and increase oxygen transfer between RBCs and between RBCs and tissues. Therefore, HBOC-201 is gradually finding applications in treating various ischemic and hypoxic diseases including traumatic hemorrhagic shock, hemolysis, myocardial infarction, cardiopulmonary bypass, perioperative period, organ transplantation, etc. However, side effects such as vasoconstriction and elevated methemoglobin caused by HBOC-201 are major concerns in clinical applications because Hbs are not encapsulated by cell membranes. This study summarizes preclinical and clinical studies of HBOC-201 applied in various clinical scenarios, outlines the relevant mechanisms, highlights potential side effects and solutions, and discusses the application prospects. Randomized trials with large samples need to be further studied to better validate the efficacy, safety, and tolerability of HBOC-201 to the extent where patient-specific treatment strategies would be developed for various clinical scenarios to improve clinical outcomes.

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Section: Trauma and Hemorrhagic Shockmentioning

confidence: 99%

New Applications of HBOC-201: A 25-Year Review of the Literature

Cao

Zhao

et al. 2021

Front. Med.

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“…A suitable biological system is the in vitro evaluation of these potential blood substitutes on human peripheral blood mononuclear cells. Indeed, once transfused into the blood vessels, blood substitutes will encounter lymphocytes, monocytes and other cells, implicated in the cellular immune response (Malkevich et al 2008). Another useful test system has previously been shown to be the culture of human umbilical vein cord cells.…”

Section: Introductionmentioning

confidence: 99%

Towards hemerythrin-based blood substitutes: Comparative performance to hemoglobin on human leukocytes and umbilical vein endothelial cells

et al. 2011

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Hemerythrin is a dioxygen-carrying protein whose oxidative/nitrosative stress-related reactivity is lower than that of hemoglobin, which may warrant investigation of hemerythrin as raw material for artificial oxygen carriers ('blood substitutes'). We report here the first biological tests for hemerythrin and its chemical derivatives, comparing their performance with that of a representative competitor, glutaraldehyde-polymerized bovine hemoglobin. Hemerythrin (native or derivatized) exhibits a proliferative effect on human umbilical vein endothelial cell (HUVEC) cultures, as opposed to a slight inhibitory effect of hemoglobin. A similar positive effect is displayed on human lymphocytes by glutaraldehyde-polymerized hemerythrin, but not by native or polyethylene glycol-derivatized hemerythrin.

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“…Neste estudo, os valores de IL-10 obtidos foram muito baixos ao longo do período de observação embora um aumento significante nos grupos HNA + Gel e HNA + NaCl foram verificados 60 minutos depois da HNA com valores médios de 59±11 pg/ml, valor que pode ser considerado normal para esta citocina nas medidas basais Nielsen et al, 2007;Malkevich et al, 2008). No estudo de Lee et al (2005) observou-se níveis de IL-10 em torno de 250 pg/ml no final da ressuscitação com gelatina e no grupo Sham.…”

Section: Grupo Controleunclassified

Avaliação da resposta inflamatória durante a hemodiluição normovolêmica aguda

Kahvegian¹

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Ao meu marido Renato, companheiro de todas as horas, pelo amor, tolerância e paciência. Ao meu irmão Marcos e minha avó Almasia pelo amor, incentivo e apoio. Aos meus pais, Antônio Carlos e Regina pela formação e educação proporcionada. Agradecimentos À Profa. Dra. Denise Tabacchi Fantoni pela inestimável orientação na realização deste trabalho, pelos ensinamentos e pela paciência. Ao Prof. Dr. José Otávio Costa Auler Jr. pelo apoio e confiança. À amiga Denise Aya Otsuki pela colaboração incomensurável, incentivo e amizade. À amiga Cristina Massoco pelos ensinamentos, idéias brilhantes, estímulo e colaboração no estudo. À Carla Holms pela imensa colaboração durante a fase experimental, fato que possibilitou a realização deste estudo. Ao Sr. Gilberto Nascimento pelo auxílio no Laboratório LIM 08 durante a fase experimental. À Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP-pelo apoio financeiro concedido e que possibilitou a realização deste estud.

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Innate Immune Response After Resuscitation With Hemoglobin-Based Oxygen Carrier and Recombinant Factor VIIA in Uncontrolled Hemorrhagic Shock in a Swine Model

Abstract: HBOC-201 + rfVIIa triggered minimum immune activation in an uncontrolled HS swine and there was a nonsignificant survival benefit.

Cited by 6 publications

References 37 publications

New Applications of HBOC-201: A 25-Year Review of the Literature

New Applications of HBOC-201: A 25-Year Review of the Literature

Towards hemerythrin-based blood substitutes: Comparative performance to hemoglobin on human leukocytes and umbilical vein endothelial cells

Avaliação da resposta inflamatória durante a hemodiluição normovolêmica aguda

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