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This Article Full Text Full Text (PDF) All Versions of this Article: 107/5/1548    most recent 00622.2009v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Cabrales, P. Articles by Palmer, A. F. PubMed PubMed Citation Articles by Cabrales, P. Articles by Palmer, A. F.

Effects of the molecular mass of tense-state polymerized bovine hemoglobin on blood pressure and vasoconstriction

¹La Jolla Bioengineering Institute, La Jolla, California; ; ²William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio; and ; ³Department of Bioengineering, University of California, San Diego, La Jolla, California

Submitted 12 June 2009 ; accepted in final form 2 September 2009

Despite recent advances in the design of hemoglobin (Hb)-based oxygen carriers (HBOCs), vasoconstriction, presumably caused by nitric oxide (NO) scavenging, vessel wall hyperoxygenation, and/or extravasation, has been identified as the principal road block hampering commercial development of HBOCs. This study was designed to analyze systemic and microvascular responses to the molecular mass and plasma concentration of tense (T)-state polymerized bovine Hb (PolybHb) solutions. Experiments were performed using the hamster window chamber model subjected to successive hypervolemic infusions of T-state PolybHb solutions. PolybHb plasma concentrations were evaluated, namely, 0.5, 1.0 and 1.5 g/dl, respectively. Infusion of PolybHb solutions with molecular mass >500 kDa elicited hypertension and vasoconstriction proportional to the plasma concentration and inversely proportional to the PolybHb cross-link density. However, two high-molecular mass PolybHb solutions, PolybHb(40:1)_high PolybHb(50:1)_high, did not elicit vasoconstriction at all concentrations studied, whereas PolybHb(50:1)_high only elicited moderate hypertension at the highest concentration studied. In contrast, infusion of PolybHb solutions with molecular mass <500 kDa elicited significant hypertension and vasoconstriction compared with PolybHb solutions with molecular mass >500 kDa that was proportional to the plasma concentration and inversely proportional to the PolybHb cross-link density. We present promising results for highly cross-linked T-state PolybHb solutions with molecular mass >500 kDa [PolybHb(40:1)_high PolybHb(50:1)_high], which supports the concept that HBOC size/molecular mass influences its proximity to the vascular endothelium and molecular diffusivity. The hemodynamics of HBOC within the plasma layer surrounding the abluminal side endothelium regulates NO production and consumption, vessel oxygen flux, and extravasation. Although mechanistically attractive, neither of these hypotheses can be directly tested in vivo and will require further investigation.

microcirculation; polymerized hemoglobin; blood substitute; hemoglobin-based oxygen carrier; functional capillary density; oxygen affinity; molecular weight; hypertension