title: Development of zero-link polymers of hemoglobin, which do not extravasate and do not induce pressure increases upon infusion.
abstract: Intramolecular crosslink of hemoglobin tetramers solved the problem of urine elimination and short intravascular retention time of cell free hemoglobin infusion. It also produced a family of crosslinked hemoglobins with P50 between 18 and 30 mmHg. However, it did not solve the problem of MAP increases in infused animals. It was proven that extravasation of hemoglobin into interstitial fluid was responsible for MAP increases. Extravasation and the MAP increase was avoided using a hemoglobin polymer with average size near 25 MDa. In spite of a very high oxygen affinity, this polymer delivered oxygen to tissues, producing either vasodilation or vasoconstriction according to oxygen needs. It was also proven that cell free hemoglobins are more efficient than red cells in delivering oxygen to tissues.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland Medical School, Baltimore, Maryland, USA. ebucci@umaryland.edu
authors.forename: Enrico
authors.initials: E
authors.lastname: Bucci
authors.forename: Herman
authors.initials: H
authors.lastname: Kwansa
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Koehler
authors.forename: Barbara
authors.initials: B
authors.lastname: Matheson
mesh_terms: D000818:Animals; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects*; D001802:Blood Substitutes / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D002415:Cats; D002417:Cattle; D003432:Cross-Linking Reagents; D006454:Hemoglobins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D008970:Molecular Weight; D010100:Oxygen / Q000378:metabolism; D011108:Polymers; D011817:Rabbits; D051381:Rats
chemical_list: D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D006454:Hemoglobins; D011108:Polymers; C079129:hemoglobin polymer; D010100:Oxygen