Hæmoglobin Solution as a Blood Substitute

O'Shaughnessy, Laurence; Mansell, H.E.; Slome, David

doi:10.1016/s0140-6736(00)71852-6

Cited by 25 publications

(6 citation statements)

References 3 publications

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“…During the past decade considerable interest has been aroused in the possibility of utilizing hemoglobin solutions as a plasma or blood substitute (9,12,29,30). It has been pointed out that such solutions would not only exert colloid osmotic pressure in the restoration of blood volume but would also possess the ability to transport oxygen.…”

Section: Resultsmentioning

confidence: 99%

“…This latter viewpoint holds that the presence of heme pigments in the plasma and urine is merely an incidental finding (6). It has been supported by a number of reports on the intravenous administration of hemoglobin solutions to the human (7)(8)(9)(10)(11)(12) which generally agree that hemoglobin can be administered without untoward reaction, although no data on acute renal functional studies have been reported. Recently, however, Amberson and associates (13) have reported late and persistent decreases in renal clearances in a single hypertensive subject following the injection of hemoglobin.…”

mentioning

confidence: 98%

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The Effect of Hemoglobin on Renal Function in the Human

Miller¹,

McDonald²

1951

J. Clin. Invest.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 98%

The Effect of Hemoglobin on Renal Function in the Human

Miller¹,

McDonald²

1951

J. Clin. Invest.

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“…The primary functional requirement of such substitutes is that they not only provide blood volume but also adequately deliver oxygen to the tissues. The use of cell-free solutions of hemoglobin (Hb) as a potential oxygen-carrying red-cell substitute has been investigated for decades (1). Purified Hb has seen shown to efficiently transport oxygen in animals without appreciable toxicity (2).…”

mentioning

confidence: 99%

Expression of fully functional tetrameric human hemoglobin in Escherichia coli.

Hoffman¹,

Looker²,

Roehrich³

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

223

135

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Synthetic genes encoding the human alpha- and beta-globin polypeptides have been expressed from a single operon in Escherichia coli. The alpha- and beta-globin polypeptides associate into soluble tetramers, incorporate heme, and accumulate to greater than 5% of the total cellular protein. Purified recombinant hemoglobin has the correct stoichiometry of alpha- and beta-globin chains and contains a full complement of heme. Each globin chain also contains an additional methionine as an extension to the amino terminus. The recombinant hemoglobin has a C4 reversed-phase HPLC profile essentially identical to that of human hemoglobin A0 and comigrates with hemoglobin A0 on SDS/PAGE. The visible spectrum and oxygen affinity are similar to that of native human hemoglobin A0. The recombinant protein shows a reduction in Bohr and phosphate effects, which may be attributed to the presence of methionine at the amino termini of the alpha and beta chains. We have also expressed the alpha- and beta-globin genes separately and found that the expression of the alpha-globin gene alone results in a marked decrease in the accumulation of alpha-globin in the cell. Separate expression of the beta-globin gene results in high levels of insoluble beta-globin. These observations suggest that the presence of alpha- and beta-globin in the same cell stabilizes alpha-globin and aids the correct folding of beta-globin. This system provides a simple method for expressing large quantities of recombinant hemoglobin and allows facile manipulation of the genes encoding hemoglobin to produce functionally altered forms of this protein.

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“…No adequate tests exist for the detection of stroma material, since the substance has not been sufficiently characterized chemically. We found that simple addition of salt to the laked cell suspension (8,13,15,17,18) did not remove all material precipitable by toluene or by acid at a pH of 5.9. Cooling the laked cell suspension and bubbling carbon dioxide through it precipitated the stroma material, but the precipitate was so fine that frequently it was impossible to separate it by filtration from the solution, and it blocked a Seitz filter pad.…”

Section: Discussionmentioning

confidence: 89%

“…(Received for publication, September 3, 1947) The infusion of hemoglobin solutions to replace lost blood has been tested in experiments on both animals (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) and man (4,(16)(17)(18)(19). Beneficial results have been obtained in restoring the volume of circulating blood, in carrying oxygen to the tissues (3), and in supplying iron for regeneration of erythrocytes and nitrogen for regeneration of blood and tissue proteins (12).…”

Section: (From the United States Navy Research Unit At The Hospital Of The Rockefellermentioning

confidence: 99%

Preparation of Hemoglobin Solutions for Intravenous Infusion

Hamilton¹,

Farr

Hiller³

et al. 1947

Journal of Experimental Medicine

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The infusion of hemoglobin solutions to replace lost blood has been tested in experiments on both animals (2-15) and man (4,(16)(17)(18)(19). Beneficial results have been obtained in restoring the volume of circulating blood, in carrying oxygen to the tissues (3), and in supplying iron for regeneration of erythrocytes and nitrogen for regeneration of blood and tissue proteins (12). For infusions hemoglobin solutions have advantages over whole blood in that the former do not need to be typed and cross-matched, and that longer preservation is possible. However, in both patients and'~mlmMs, some of the infusions have been followed by unfavorable results, particularly on the kidneys. It has appeared uncertain whether these effects have been due to injury by the hemoglobin itself, caused during its rather rapid excretion through the kidneys, to admiTture of methemoglobin with the active hemoglobin (hemoglobin capable of reversible combination with oxygen), to the presence of cell stroma material in the hemoglobin solutions used, or to bacterial contamination or products.The present work was undertaken to provide a method whereby large volumes of hemoglobin solution could be prepared in a sterile state, free from stroma material, of electrolyte content approximating that of plasma, and capable of preservation without change of the active hemoglobin to methemoglobin. Analytical Methods and TestsThe carbon monoxide-blnding capacity of the hemoglobin solutions was determined by a modification of the method of Van Slyke and Hiller (20) described by Van Slyke, Hiller,

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Hæmoglobin Solution as a Blood Substitute

Cited by 25 publications

References 3 publications

The Effect of Hemoglobin on Renal Function in the Human

The Effect of Hemoglobin on Renal Function in the Human

Expression of fully functional tetrameric human hemoglobin in Escherichia coli.

Preparation of Hemoglobin Solutions for Intravenous Infusion

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