Hemoglobin substitutes

Manley GT, Hemphill JC, Morabito D, et al. Small-volume resuscitation with the hemoglobin substitute HBOC-201 effect on brain tissue oxygenation. Adv Exp Med Biol 2003 530 311. 

Another hemoglobin substitution product, liposome-encapsulated tetrameric hemoglobin, can exacerbate the manifestations of septic shock (2). 

About 75% of hemoglobin is in the form of an a-helix and 25% is a random coil form. Certain amino acid substitutions could shift the equilibrium between the a-helix and the random coil, thereby altering tertiary structure (Chou and Fasman, 1974). One such substitution is proline, which cannot participate in an a-helix (except as one of the first three residues). Hemoglobins Duarte and Madrid have a proline substitution for alanine, while eight other hemoglobins substitute proline for leucine. 

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). 

Cell-Free Hemoglobin. Hemoglobin seems to be the logical choice for a red cell substitute because of its high capacity to carry oxygen (Fig. 

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. 

Abnormal Hemoglobin Normal Residue and Position Substitution... 

Many are distinguished from Hb-A by electrophoretic or chromatographic methods The number and types of abnormal hemoglobins that have been discovered thus far are Indeed overwhelming At the latest count (December, 1974) at least 135 3-chaln variants, 72 a-chaln variants, 8 6-chaln variants, and 11 y-chaln variants have been found These Include variants with single amino acid substitutions (the majority), variants with two substitutions (the 6-chaln variants, Hb-C-Harlem and Hb-Arllng-ton Park), variants with deletion of one or more residues... 

Detection of Variants With Altered Functional Properties. When substitutions In either a-or 3-chains Involve amino acid residues that participate In the contact with heme or the contact between chains, changes In functional properties can occur and the determination of the oxygen affinity of the blood sample or of an Isolated hemoglobin variant Is desirable. Oxygen affinity Is affected by temperature, pH, salt concentration, the level of 2,3-dlphosphoglycerate (2,3-DPG), and to a lesser extent by the concentration of the hemoglobin. The concentration of 2,3-DPG In blood changes rather rapidly after collection and a... 

Sickle hemoglobin A defective form of hemoglobin produced as a result of a single substitution of the amino acid valine for glutamic acid at position 6 of the (1-polypeptide chain. 

Sickle cell disease is caused by a mutation that results in the substitution of a valine residue for a glutamate residue in the sixth position of the hemoglobin P-chain. This results from the substitution of a T for an A in the glutamate codon. When (1) DNA from a patient... 

Early in the search for myoglobin or hemoglobin model compounds for study, it was learned that cobaltoheme substituted into apo—myoglobin or -hemoglobin... 

Rudolf and Cliff [3.43] described the inclusion of hemoglobin in liposomes (LEH), to produce a stable blood substitute. The liposomes were formed from a solution of soya bean - phosphatidylcholine (soy PC), cholesterol, dimyristoyl-phosphatidyl, DL-glycerol (DMPG), and alpha-tocopherol with a ratio of 10 9 0.9 0.1. The product was dried and... 

H. E. Zemel and B. M. Hoffman, Long-range triplet-triplet energy transfer within metal-substituted hemoglobins, J. Not. Chem. Soc. 103, 1192-1201 (1981). 

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