Biological oxygen-carrying therapeutic agents: Roles and applications / 中国组织工程研究

BACKGROUND: Although blood donation by healthy people can relieve the urgent need of clinical blood to some extent, it is impossible to fundamentally solve the problem of blood shortage and blood safety by relying solely on blood donation by healthy people. OBJECTIVE: In combination with the significance of the development of biological oxygen-carrying therapeutics, to expound the unique characteristics of biological oxygen-carrying therapeutics, and to summarize the research status and application progress of biological oxygen-carrying therapeutics in recent years, in order to provide a certain theoretical basis for further research on the role and clinical application of biological oxygen carrying therapeutic agents. METHODS: The authors searched the relevant articles published from January 2015 to August 2019 in the databases of CNKI, Wanfang and PubMed. The keywords were “blood substitute, hemoglobin oxygen carrier, artificial blood, oxygen-carrying therapeutic agent” in English and Chinese. Types of search literature included original research and reviews. Initially 418 articles were included, and finally 46 eligible articles were classified and reviewed. RESULTS AND CONCLUSION: The biological oxygen-carrying therapeutic agent has a good clinical effect. It can maintain blood osmotic pressure, acid-base balance and blood volume, and also has good oxygen-carrying capacity. It can deliver oxygen to local hypoxic tissue for a long time. It is also easy to store and transport. Biological oxygen-carrying therapeutic agents have been widely used in surgery, which are of great help to expand blood volume and accelerate postoperative recovery. Therefore, the development of biological oxygen-carrying therapeutic agents is of great significance for surgical trauma and resuscitation, hemorrhagic shock, malignant anemia, myocardial infarction and other diseases. It shows a good clinical application prospect.

Tinjauan Perkembangan Penghasilan Pengganti Darah (A Review on Development of Blood Substitute) / Jurnal Sains Kesihatan Malaysia

@#This review paper aims to present an overview of the development of blood substitute particularly red blood cell substitute or artificial oxygen carrier. Knowledge on human blood inspired from the understanding of human blood circulation system. Ibn Nafis was first to describe that blood flow through respiratory system before entering the heart. This finding denied the claim that tiny pores present within the septum of the heart. Then, William Harvey further described human cardiovascular system in detail and contributed to better understanding on the roles of blood in body. Several blood transfusions were attempted using blood collected from human, animal and other blood substitutes such as milk before the practice was banned for almost 150 years in Europe. Major discoveries on blood group and antibody reaction have made blood transfusion safer. However, several issues and challenges have re-triggered the exploration to develop red cell substitutes. Two approaches have been taken to develop the red blood cell substitute which are classified into biological and chemical based oxygen carriers. The earliest efforts have been on haemoglobin based oxygen carrier (HBOC) and perfluorocarbon (PFC) while the recent developement are on polymer-based oxygen carrier and in-vitro stem cell derived red blood cell.

A review of blood substitutes: examining the history, clinical trial results, and ethics of hemoglobin-based oxygen carriers

The complications associated with acquiring and storing whole blood for transfusions have launched substantial efforts to develop a blood substitute. The history of these efforts involves a complicated mixture of science, ethics, and business. This review focuses on clinical trials of the three hemoglobin-based oxygen carriers (HBOC) that have progressed to Phase II or III clinical trials: HemAssist (Baxter; Deerfield, IL, US), PolyHeme (Northfield; Evanston, IL, US), and Hemopure (Biopure; Cambridge, MA, US). Published animal studies and clinical trials carried out in a perioperative setting have demonstrated that these products successfully transport and deliver oxygen, but all may induce hypertension and lead to unexpectedly low cardiac outputs. Overall, these studies suggest that HBOCs resulted in only modest blood saving during and after surgery, no improvement in mortality and an increased incidence of adverse reactions. To date, the results from these perioperative studies have not led to regulatory approval. All three companies instead chose to focus their efforts on large trials of trauma patients in the pre-hospital setting. Baxter abandoned the development of HemAssist after a trial in the U.S. was prematurely halted when the first 100 patients showed significantly increased mortality rates as compared to patients treated with blood products. Northfield's PolyHeme trial demonstrated a non-significant trend towards increased mortality and a very modest reduction in the subsequent need for blood. The testing of Biopure's Hemopure for trauma patients has been halted for several years because of FDA concerns over trial design and study justification. Ethical concerns have also been raised regarding the design and implementation of all HBOC clinical trials. Thus, the available evidence suggests that HemAssist, Polyheme, and Hemopure are associated with a significant level of cardiovascular dysfunction. The next generation of HBOCs ...

Current Status and Future of Artificial Blood: Focusing on Red Blood Cell Substitutes

Blood substitutes, especially red blood cell (RBC) substitutes, have been developed for the past five decades and have several advantages over allogenic packed RBCs, including a prolonged half-life, lack of a cross-matching requirement, and minimal infection risk or concerns about immunologic reactions. There are two main groups in RBC substitutes: perfluorochemicals and hemoglobin-based oxygen carriers (HBOCs). HBOCs are made of hemoglobins from: human, bovine or recombinant and undergo three modification types: chemical (intramolecular cross-linking, polymerization, conjugation to macromolecules and combination of several chemical modifications), genetic, or technological (microencapsulation). The types, side effects, current status of clinical trials, and the future of HBOCs are described in details.

Current Status and Future of Artificial Blood: Focusing on Red Blood Cell Substitutes

Blood substitutes, especially red blood cell (RBC) substitutes, have been developed for the past five decades and have several advantages over allogenic packed RBCs, including a prolonged half-life, lack of a cross-matching requirement, and minimal infection risk or concerns about immunologic reactions. There are two main groups in RBC substitutes: perfluorochemicals and hemoglobin-based oxygen carriers (HBOCs). HBOCs are made of hemoglobins from: human, bovine or recombinant and undergo three modification types: chemical (intramolecular cross-linking, polymerization, conjugation to macromolecules and combination of several chemical modifications), genetic, or technological (microencapsulation). The types, side effects, current status of clinical trials, and the future of HBOCs are described in details.

Visualization of Pulsatile Flow of the Blood Substitute Fluids Using the Particle Image Velocimetry

PURPOSE: The objective of the present study is to investigate the steady and pulsatile flow phenomena of the blood substitute fluids in the circular and bifurcated vessels numerically and experimentally. METHODS: The particle image velocimetry (PIV) is adopted to visualize the flow fields in the circular and bifurcated vessels. In order to analyse the complex flow phenomena of the blood substitute fluids in the bifurcated vessel, the constitutive equations which are suitable to describe the rheological properties of the non-Newtonian fluids are determined and the steady and unsteady momentum equations are solved by the finite volume prediction. RESULTS AND CONCLUSION: Velocity vectors of the steady flow in the bifurcated tube obtained by the PIV system are in good agreement with those obtained by the numerical analysis. The experimental and numerical results show the recirculation zone in the outer wall distal to bifurcation.

Metabolism of an isolated brain perfused with perfluoro blood substitute.

An unanesthetized, isolated, perfused rat brain, consisting of the skull and its contents with nearly all other tissues removed, has metabolic and electrical activity similar to that of the brain of the intact rat with its blood-brain barrier intact. Its use yielded results that are difficult or impossible to obtain from in vitro preparations or in vivo. With the perfused brain it was shown that, mannose can completely replace glucose as metabolic substrate, that insulin has no direct effect on the brain, in the absence of added substrate glutamate is metabolized to aspartate, the brain does not metabolize ethanol, and morphine probably inhibits mitochondrial oxidative activity. Since the use of a perfluoro blood substitute to perfuse the brain avoids the optical interference caused by haemoglobin, it was possible to measure changes in the oxidation-reduction state of NADH by surface fluorometry of the cerebral cortex.

CHRONIC TOXIC PATHOLOGIC INVESTIGATION OF FLUOROCARBON BLOOD SUBSTITUTE / 第二军医大学学报

Fluorocarbon emulsion, a substitute of blood, 20 ml/kg were injected once into dogs intravenously. As a result, part of the substitute deposited in the lympho-retic-ular system and was phagocytized by fixed and free histiocytes (rnonophagocytic system), and the histiocytes then converted into foaming cells.One month after injection, the fluorocarbon's deposits in the foaming cells remained at the peak level in the liver, spleen and other organs of the lympho-reti-cuJar system. After six months,no deposits could be found in all viscera and no signs of any pathological changes, except the spleen under a light microscope.After twelve months, no foaming cells were found in the spleen, liver, and kidney under light cmicroscope,yet but foaming cells could be found in the spleen and liver with the help of an electron microscope and we believed that this sign had no pathological significance in clinic practice.The target cells only showed the action of phagocitizing and depositing.According to our observation, the fluorocarbon emulsion is a non cytoplasmic toxin and an inert biologic substance, so there are no secondary histo-pathologic changes caused by fluorocarbon deposition. It seems that 20 ml/kg of fluorocarbon emulsion (equal to 1200 ml for adult human)injected intravenously is rather safe.