Oxygen-carrying blood substitutes

Thus far, the only molecules that have found even a limited clinical application as an oxygencarrying blood substitute are the fluorocarbons and haemoglobin. 

Pyridoxal 5 -phosphate (a derivative of pyridoxal vitamin Bg) is similar in size and charge to 2,3-DPG. Covalent attachment of pyridoxal 5 -phosphate reduces the oxygen affinity of the haemoglobin molecule. Covalent attachment of benzene isothiocyanates to the amino termini of the four haemoglobin polypeptide chains, also yields derivatives which display lower oxygen affinity. These may prove worthy of clinical investigation. 

In addition to altered oxygen-binding characteristics, free haemoglobin in plasma disassociates rapidly into afi dimers, which are in turn rapidly oxidized and cleared by the kidneys. Indeed, high plasma concentrations can result in kidney toxicity. Development of a 

Although research continues in an effort to develop an effective haemoglobin-based red blood cell substitute, no suitable candidate has yet been developed that has gained widespread clinical acceptance. 

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Figure 9-19. Three-dimensional structure of the seram albumin including iron porphyrins as an oxygen-carrying blood substitute.

Kobayashi K, Tsuchida E, Nishide H. Totally synthetic hemes their characteristics and oxygen carrying capacity in dogs. In Tsuchida E, ed. Artificial Red Cells Materials, Performances and Clinical Study as Blood Substitutes. Chichester, England John Wiley Sons Ltd., 1995 93. 

Fig. 17.4 The comparison of the costs of several blood substitutes companies to develop an oxygen carrying molecule vs. the Alios Therapeutics Inc. allosteric effector RSR 13 to an IND and phase one clinical trial.

Blood Substitutes. Researchers in lapan (Fukushima Medical Center) and in other institutions in Europe and North America have been investigating substances that, in major characteristics, may serve as a substitute for blood, particularly in emergency situations where rare blood types are not immediately available to severely ill patients who require transfusions. For example, in early 1979, a lapanese patient with a rare O-negative blood was given an infusion of one liter of a new, oxygenated perfluorocarbon emulsion. This compound carried oxygen through the patient s circulatory system until the rare blood could be obtained. 

Hetastarch is a plasma expander that produces expansion of plasma volume. It does not have oxygen-carrying capacity or contain plasma protein, so it is not a blood or plasma substitute. It is indicated as an adjunct therapy for plasma volume expansion in shock caused by hemorrhage, bums, surgery, sepsis, or other trauma and as an adjunct in leukapheresis to improve harvesting and increase yield of granulocytes. 

We have synthesized several kinds of retrievable nanoreactor materials for use as potential blood substitutes. Because of the large volumes needed clinically, and the rapid circuit time of blood in the body, continuous magnetic retrieval and immunoflltration are simple not practical methods for retrieval. Therefore, we focused on high buoyant density oxygen-carrying retrievable nanoreactors. Such materials could be separated in continuous fashion using clinically accepted aphaeresis units, cell savers and similar technologies. 

Blood transfusion or the introduction of blood substitutes is usually preceded by the anemic phase where blood is hemodiluted to maintain volume with non-oxygen-carrying crystalloids or colloids. This phase introduces changes in the mechanical and chemical environment of the endothelium, which propagate upon transfusion. These changes include activation of genetically controlled mechanisms such as endothelial impairment due to inflammatory reactions [80], activation of the endothelium, platelets, and neutrophils, and liberation of cytokines. At the cellular level, there may be endothelial swelling and increased endothelial permeability due to ischemic injury [55]. 

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