Salvage of focal cerebral ischemic damage by transfusion of high O 2-affinity recombinant hemoglobin polymers in mouse

Masaaki Nemoto, Toshiaki Mito, William S. Brinigar, Clara Fronticelli, Raymond C. Koehler

Research output: Contribution to journalArticlepeer-review

Abstract

Cell-free hemoglobin solutions with high oxygen affinity might be beneficial for selectively delivering oxygen to ischemic tissue. A recombinant hybrid hemoglobin molecule was designed using the human α-subunit and the bovine β-subunit, with placement of surface cysteines to permit disulfide bond polymerization of the tetramers. The resulting protein generated from an Escherichia coli expression system had a molecular mass >1 MDa, a P 50 of ∼3 Torr, and a cooperativity of n = 1.0. Anesthetized mice were transfused during 2-h occlusion of the middle cerebral artery. Compared with transfusion with 5% albumin, cerebral infarct volume was reduced by 41% with transfusion of a 3% solution of the high oxygen-affinity hemoglobin polymer and by 50% with transfusion of a 6% solution of the polymer. Transfusion of a 6% solution of a 500-kDa polymer possessing a P50 of 17 Torr and a cooperativity of n = 2.0 resulted in a 66% reduction of infarct volume. These results indicate that cell-free Hb polymers with P50 values much lower than that of red blood cell hemoglobin are highly capable of salvaging ischemic brain. The assumption that the P50 of blood substitutes should be similar to that of blood might not be warranted when used during ischemic conditions.

Original languageEnglish (US)
Pages (from-to)1688-1691
Number of pages4
JournalJournal of applied physiology
Volume100
Issue number5
DOIs
StatePublished - May 2006

Keywords

  • Blood substitute
  • Cerebral ischemia
  • Middle cerebral artery
  • Oxygen carrier

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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