Salvage of focal cerebral ischemic damage by transfusion of high O2-affinity recombinant hemoglobin polymers in mouse.

J Appl Physiol (1985)

Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.

Published: May 2006

AI Article Synopsis

  • The study explores cell-free hemoglobin solutions designed to improve oxygen delivery to areas of reduced blood flow (ischemic tissue).
  • Researchers created a recombinant hemoglobin using human and bovine components, achieving a high molecular mass and oxygen affinity (P50 of about 3 Torr).
  • In tests on anesthetized mice, the new hemoglobin solution significantly reduced brain tissue damage compared to standard treatments, suggesting lower P50 values might be more effective for oxygen delivery during ischemic events.

Article 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 alpha-subunit and the bovine beta-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 P50 of approximately 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1764455PMC
http://dx.doi.org/10.1152/japplphysiol.01374.2005DOI Listing

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