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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3603-3610.
Prepublished online as a Blood First Edition Paper on July 20, 2006; DOI 10.1182/blood-2006-02-005272.
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Submitted February 27, 2006
Accepted June 29, 2006
DISSOCIATION OF LOCAL NITRIC OXIDE CONCENTRATION AND VASOCONSTRICTION IN THE PRESENCE OF CELL-FREE HEMOGLOBIN OXYGEN CARRIERS
Amy G. Tsai*, Pedro Cabrales, Belur N. Manjula, Seetharama S. Acharya, Robert M. Winslow, and Marcos Intaglietta
University of California, San Diego and La Jolla Bioengineering Institute, San Diego, La Jolla, CA
La Jolla Bioengineering Institute, San Diego, La Jolla, CA
Departments of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY
Departments of Physiology and Biophysics, Albert Einstein School of Medicine, Bronx, NY
Sangart Inc., San Diego, CA
University of California, San Diego and La Jolla Bioengineering Institute
* Corresponding author; email: agtsai{at}ucsd.edu.
Cell free hemoglobin's (CFH) high affinity for nitric oxide (NO) could limit its 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 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)  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 except for PEG-Hb which caused blood volume expansion due to its higher colloid osmotic pressure. 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.
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