Widespread clinical use of acellular hemoglobin (Hb)-based O2 carriers (HBOCs) has been hampered by their
ability to elicit both vasoconstriction and systemic hypertension. This is primarily due to the ability of acellular Hb to extravasate
through the blood vessel wall and scavenge endothelial-derived nitric oxide (NO). Encapsulation of Hb inside
the aqueous core of liposomes retards the rates of NO dioxygenation and O2 release, which should reduce or eliminate the
vasoactivity of Hb. Our aim is to determine the extent of systemic and microvascular vasoactive responses (hypertension,
vasoconstriction and hypoperfusion) after infusion of vesicle encapsulated Hbs, in which the encapsulated Hb is in either
the deoxygenated or carbon monoxide (CO) state (HbV and COHbV, respectively). To investigate this hypothesis, we
used the hamster window chamber model subjected to two successive hypervolemic infusions of HbV and COHbV solutions
(each infusion represents 10% of the animal’s calculated blood volume) at Hb concentrations of either 7 or 10 g/dL.
The hypervolemic infusion model used in this study has all the regulatory mechanisms responsible for predicting the
vasoconstrictive responses of HBOCs. The results of this study demonstrate the absence of vasoconstrictive and hypertensive
responses upon single and multiple infusions of HbV and COHbV solutions. The HbV and COHbV solutions increased
the plasma O2 carrying capacity. However, COHbV delivered low therapeutic levels of CO without inducing any
microcirculatory disturbances. Significance: Vesicles containing Hb can be used as a new therapeutic agent in transfusion
medicine to treat anemia and revert hypoperfusion.
Keywords: Blood pressure, functional capillary density, hemoglobin-based oxygen carrier, hypertension, microcirculation, red
blood cell substitute, vasoconstriction, vesicle encapsulated hemoglobin, Hemoglobin Encapsulated Poly(Ethylene Glycol), COHbV.
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Published on: 10 July, 2012
Page: [224 - 234]