The Ability of Polyethylene Glycol Conjugated Bovine Hemoglobin (PEG-Hb) To Adequately Deliver Oxygen in Both Exchange Transfusion and Top-Loaded Rat Models

Abstract

The purpose of this study was to determine whether a six gram percent (g%) solution of the hemoglobin based oxygen carrier, polyethylene glycol conjugated bovine hemoglobin (PEG-Hb) could adequately deliver oxygen in both partial exchange transfusion and top-loaded rat models. This study measured tissue oxygen tension, circulatory retention and cardiovascular effects following both 30% exchange transfusion and 20 to 25 mL/kg top-loaded infusions of PEG-Hb. Oxygen delivery to rat tissues was determined using an oxygen dependent phosphorescence quenching method (Oxyspot). Telemetric intravascular blood pressure probes monitored heart rate and mean arterial pressure. In both models, six g% PEG-Hb (P50-15 torr) was shown to oxygenate tissue better than stroma-free bovine Hb (P50-26 torr), cross-linked bovine Hb (P50-48 torr) or simple plasma expanders. The mean circulatory half life of PEG-Hb was 15.0 +/- 2.3 hours and 17.4 +/- 1.6 hours for exchange transfusion and 25 mL/kg top-loaded rat models, respectively. Mean arterial pressure (MAP) in PEG-Hb treated rats was insignificantly different from sham controls undergoing a 30% exchange transfusion or following a top-loaded infusion. In conclusion, the PEG conjugated form of bovine Hb with its relatively long vascular persistence may possess characteristics that facilitate tissue oxygenation in the rat.

Effect of oxygen affinity and molecular weight of HBOCs on cerebral oxygenation and blood pressure in rats

“…The direct vasoactive effect of different HBOCs appears to be inversely related to their MW which suggests that small molecules are more vasoconstricting. [15][16][17] Clinical and experimental studies suggest that the order of vasoreactivity is highest for the smaller MW HBOCs including diaspirin cross-linked hemoglobin, moderate for polymerized hemoglobins which contain a portion of small MW hemoglobins, and lowest for surface modified hemoglobins that have higher MWs. 26 The current study supports this hypothesis within a single group of chemically modified HBOCs.…”

“…This suggests that small HBOC molecules are more vasoconstricting. [15][16][17] Presumably, pronounced vasoconstriction would be disadvantageous because it could limit optimal delivery of oxygen to tissues.…”

A novel hemoglobin-based blood substitute protects against myocardial reperfusion injury

“…The Bohr effect has also been shown to be more pronounced in bovine Hb, which allows an even better O 2 delivery at lower pH values. It has also been shown that this blood substitute does not change hemodynamics with respect to PCO 2 and pH (1,6,12,17,19,23). HBOC-201 is modified by cross-linking of the ␣,␤-dimers to form a tetrameric structure that does not dissociate as rapidly as free Hb (14).…”

Haemoglobin Hyperpolymers, a New Type of Artificial Oxygen Carrier – Concept and Current State of Development

“…Additionally, the primary structures of these substances are very similar [15]. The synthesised blood additive exhibits a p50 value of 16 mm Hg and a cooperativity of 2.1, which, according to Conover et al [6], results in optimised conditions for oxygen release. An effective concentration of the carrier of approximately 3 g/dl in blood plasma is reasonable.…”

“…A further very important property is an optimal oxygen affinity, which is not even found in normal blood which exhibits a half-saturation pressure (p50) of approximately 25 mm Hg. Investigations carried out by Conover et al [6] showed that the provision of oxygen to organs by means of plasmatic oxygen carriers occurs best when these agents exhibit a half-saturation pressure of between 15 und 20 mm Hg. The oxygen-transporting blood additive should be able to compensate for a poor tissue oxygenation whereby it is probable that the haemoglobin saturation will need to fall below 50%, as suggested by measurements of tissue oxygen partial pressure below 25 mm Hg (already in normal tissue, see e.g.…”