Hemoglobin Encapsulation With Polyethylene Glycol-modified and Unmodified Vesicles: Systemic and Microvascular Hemodynamics at 80% Blood Substitution

Abstract

Phospholipid vesicles containing purified hemoglobin (Hb vesicles, HbV) of high stability and uniform size have been developed to provide oxygen carrying capacity to plasma expanders. Their function as a blood replacement was tested in exchange transfusion where 80% of the red blood cell mass was substituted with suspensions of vesicles in 5% human serum albumin (HSA) solution. Vesicles were tested with membranes that were unmodified (HbV) or conjugated with polyethylene glycol (PEG-HbV). Both materials yielded normal systemic hemodynamic conditions at all levels of exchange which could not be achieved with HSA alone. Subcutaneous microvascular studies in awake hamsters showed that PEG-HbV yielded significantly improved microhemodynamic conditions relative to unmodified HbVs. The tissue oxygenation was lower than in the blood-perfused microcirculation. These results highlight the significance of microvascular analysis in the study and design of blood substitutes, while the development and availability of these vesicles provides a unique opportunity to determine the optimal set of parameters needed to design a blood substitute.