Blood substitute

Blood substitutes, as defined here, refers to any substance which can  

Dextran 1 Dextran 40 Dextran 60 Dextran 70 Dextran 110 Gelatin 

The majority of blood substitutes currently in use function only as plasma expanders. These maintain blood pressure by providing vascular fluid volume after haemorrhage, burns, sepsis or shock. While standard electrolyte solutions, such as physiological saline, may be administered, their elfect is transitory as they subsequently dilfuse back out of the vascular system. 

Alternatively, colloidal plasma expanders (Table 9.3) are used. When administered at appropriate concentrations, they exert an osmotic pressure similar to that of plasma protein, hence vascular volume and blood pressure are maintained. The major disadvantages of colloidal therapy include its relatively high cost, and the risk of prompting a hypersensitivity reaction. Determined elforts to develop blood substitutes were initiated in 1985 by the US military, concerned about the issue of blood supply to future battlefields. 

Higher molecular mass dextrans (partieularly dextran 70, 75 and 110) are used to promote short-term expansion of plasma volume thus preventing/treating shoek due to blood loss. A 6% w/v solution of these dextrans exerts an osmotie pressure similar to that of plasma proteins. Generally, an initial dose of 500 ml 1 litre is administered by i.v. infusion. Dextrans also inhibit the aggregation of red blood eells. Thus, they are often used to prevent/treat post-operative thrombo-embolic disorders (see later in this ehapter) and to improve blood flow. 

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Medical appHcations of PFC emulsions for organ perfusion and intravenous uses have received much attention in recent years. The first commercial blood substitute (Fluosol DA 20%, trademark of the Green Cross Corp.) employed perfluorodecalin, and improved, second generation products based on this PFC, or perfluorooctylbromide, are now under development (20,21). The relatively high oxygen dissolving capabiHty of PFCs undedies these appHcations (see Blood, artificial). 

Perfluorinated compounds are also potentially useful as inert reaction media, particularly when one of the reactants is gaseous. The high solubiHty of oxygen and carbon dioxide in perfluorinated Hquids has allowed their use as blood substitutes (41) and as oxygenation media for biotechnology (42). One product, Fluosol DA (43) (Green Cross Corp.), has been commercialized, and there is an abundant patent art in this area (see Blood, artificial). 

Other biomedical and biological appHcations of mictocapsules continue to be developed. For example, the encapsulation of enzymes continues to attract interest even though loss of enzyme activity due to harshness of the encapsulation protocols used has been a persistent problem (59). The use of mictocapsules in antibody hormone immunoassays has been reviewed (60). The encapsulation of hemoglobin as a ted blood substitute has received much attention because of AIDS and blood transfusions (61). 

T. M. S. Chang, ed.. Blood Substitutes and Oxygen Carriers, Marcel Dekker, New York, 1992. 

The idea of red cell substitutes is not new. In Ovid s Metamorphosis the witch Medea restored Jason s aged father, Aeson, by slitting his throat to let out old blood, replacing it with a magic brew she had concocted (1). Sir Christopher Wren was one of the first to apply the new knowledge about circulation to blood substitutes. In 1656 he infused ale, wine, scammony, and opium into dogs and from these efforts conceived the ideal of transfusing blood from one animal to another. Lower actually carried out the first transfusion experiments (2). 

Albumin. Investigation iato the safety of bovine plasma for clinical use was undertaken ia the eady 1940s ia anticipation of wartime need (26). Using modem proteia chemistry methods, including electrophoresis and ultracentrifugation, it was shown that most of the human adverse reactions to blood substitutes were caused by the globulin fraction and that albumin was safe for parenteral use. Human albumin is now used extensively as a plasma expander ia many clinical settings. 

AH of the reactions considered to be useful in the production of hemoglobin-based blood substitutes use chemical modification at one or more of the sites discussed above. Table 2 Hsts the different types of hemoglobin modifications with examples of the most common reactions for each. Differences in the reactions are determined by the dimensions and reactivity of the cross-linking reagents. Because the function of hemoglobin in binding and releasing... 

In 1982 a study of the usefulness of DBBF in the production of a blood substitute was reported (99). A single modification achieved the dual goals of reduced oxygen affinity and restricted tetramer—dimer dissociation. This work was confirmed in 1987 (98). The product, called aa-hemoglobin, was formulated in Ringer s lactate. P q under physiologic conditions is 3.7 kPa (28.0 torr). Hill s parameter is 2.2, and the Bohr effect was reduced (100). Plasma retention was increased, and the product appeared to be less heterogeneous than some of the other derivatives under study. Its production was scaled up by Baxter Healthcare Corp., under contract to the U.S. Army. 

Outdated Human Blood. If clinical efficacy and safety of hemoglobin solutions can be shown, the demand for product would soon outstrip the supply of outdated human blood. About 12 million units of blood (1 unit 480 mL) are used in the United States each year, and only about 500,000 outdate. The primary use of blood is in intraoperative and emergency settings. The quantity of blood available for use in production of blood substitutes depends on safety and efficient usage of blood products as well as on the demands on blood suppHes. 

Dozens of compounds have been used in in vivo fluonne NMR and MRI studies, chosen more for their commercial availability and established biochemistry than for ease of fluonne signal detection [244] Among the more common of these are halothane and other fluormated anesthetics [245, 246], fluorodeoxyglucose [242 243], and perfluormated synthetic blood substitutes, such as Fluosol [246], a mixture of perfluorotnpropylamine and perfluorodecahn Results have been Imut-ed by chemical shift effects (multiple signals spread over a wide spectral range) and long acquisition times... 

Moore, R E, Clark, L C, Jr Proc 5th Int Symp Perfluorochem Blood Substitutes, Mainz, 1981, W Zuckschwerdt Verlag Munich, 1982, p 50... 

Polyfvinyl pyrrolidone), prepared from iV-vinylpyrrolidone, is used both in cosmetics and as a synthetic blood substitute. Draw a representative segment of the polymer. 

The direct histamine release evoked by several substances (e.g. codeine, dextran in certain rat strains or gelatine blood substitutes) led to the development of the concept of pseudo-allergic reactions by Paul Kallos [10]. 

An extreme example of slime production is found in Leuconostoc dextranicum and L. mesenteroides where so much carbohydrate, called dextran, may be produced that the whole medium in which these cells are growing becomes almost gel-like. This phenomenon has caused pipe blockage in sugar refineries and is deliberately encouraged for the production of dextran as a blood substitute (Chapter 25). 

Doenicke A., Grote B. Lorenz W. (1977) Blood and blood substitutes. Br JAnaesth, 49, 681—... 

Combat medicine poses special problems. Chemical science and technology can aid in the rapid detection and treatment of injuries from chemical and biological weapons and other new weapons such as lasers. We need to develop blood substitutes with a long shelf life, and improved biocompatible materials for dealing with wounds. For the Navy, there are special needs such as analytical systems that can sample the seawater to detect and identify other vessels. We need good ways to detect mines, both at sea and on land. Land mines present a continued threat to civilians after hostilities have ended, and chemical techniques are needed to detect these explosive devices. 

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