Endothelial Dysfunction Enhances Vasoconstriction Due to Scavenging of Nitric Oxide by a Hemoglobin-based Oxygen Carrier

• DOI: 10.1097/aln.0b013e3181cd7838
• Publication Date: 2010-02-17T07:31:01Z
• Authors: Binglan Yu; Mohd Shahid; Elena M. Egorina; Mikhail A. Sovers...; Michael J. Raher; Chong Lei; Mei X. Wu; Kenneth D. Bloch; Warren M. Zapol
• Keywords: Endothelial Dysfunction; Hypoxic pulmonary vasoconstriction; Phenylephrine

To date, there is no safe and effective hemoglobin-based oxygen carrier (HBOC) to substitute for erythrocyte transfusion. It uncertain whether a deficiency of endothelial nitric oxide bioavailability (endothelial dysfunction) prevents or augments HBOC-induced vasoconstriction.Hemodynamic effects infusion PolyHeme (1.08 g hemoglobin/kg; Northfield Laboratories, Evanston, IL) murine tetrameric hemoglobin (0.48 hemoglobin/kg) were determined in awake healthy lambs, mice, anesthetized mice. In vitro, cumulative dose-tension response was obtained by sequential addition phenylephrine-precontracted aortic rings.Infusion did not cause systemic hypertension lambs but produced acute pulmonary vasoconstriction. Infusion wild-type mice induced severe vasoconstriction with dysfunction (either db/db high-fat fed 4-6 weeks). The more sensitive than after the either PolyHeme. Murine ring studies confirmed that have an impaired endothelial-dependent vasodilator enhanced vasoconstrictor HBOC.Reduction low molecular weight concentrations less 1% insufficient abrogate HBOC sheep reduced vascular levels associated dysfunction. These findings suggest testing HBOCs animals can provide indication their potential effects.