title: Dissociation of local nitric oxide concentration and vasoconstriction in the presence of cell-free hemoglobin oxygen carriers.
abstract: Cell-free hemoglobin's (CFH) high affinity for nitric oxide (NO) could limit CFH's use as an oxygen-carrying blood replacement fluid because it scavenges NO, causing vasoconstriction and hypertension. However, the extent to which perivascular NO levels change following intravascular administration of hemoglobin (Hb) with different molecular dimensions correlates with vasoconstrictive responses in the microcirculation is unknown. The study objective was to determine vasoconstrictive effects following bolus infusions of (1) alphaalpha cross-linked Hb; (2) polymerized bovine Hb; or (3) polyethylene glycol-decorated Hb (PEG-Hb), by measurements of in vivo microvessel diameter, blood flow, perivascular NO concentration, and systemic hemodynamic parameters. All CFHs caused reductions in perivascular NO levels, not correlated to microvascular responses. PEG-Hb (largest molecular volume) maintained blood flow, while the others caused vasoconstriction and reduced perfusion. All solutions increased mean arterial pressure due to vasoconstriction and blood volume expansion, except for PEG-Hb, which increased blood pressure due to blood volume expansion and maintenance of cardiac output. In conclusion, perivascular NO reduction is similar for all Hb solutions because NO binding affinities are similar; however, effects on vascular resistance are related to the type of molecular modification, molecular volume, and oxygen affinity.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412, USA. agtsai@ucsd.edu
authors.forename: Amy G
authors.initials: AG
authors.lastname: Tsai
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
authors.forename: Belur N
authors.initials: BN
authors.lastname: Manjula
authors.forename: Seetharama A
authors.initials: SA
authors.lastname: Acharya
authors.forename: Robert M
authors.initials: RM
authors.lastname: Winslow
authors.forename: Marcos
authors.initials: M
authors.lastname: Intaglietta
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000494:pharmacology*; D006224:Cricetinae; D006454:Hemoglobins; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000097:blood*; D010100:Oxygen / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D009569:Nitric Oxide; D010100:Oxygen