Targeted O2 delivery by low-P50 hemoglobin:: a new basis for O2 therapeutics

To assess O-2 delivery to tissue by a new surface-modified, polyethylene glycol-conjugated human hemoglobin [MP4; PO2 at 50% saturation of hemoglobin (P-50); 5.4 mmHg], we studied micro-circulatory hemodynamics and O-2 release in golden Syrian hamsters hemodiluted with MP4 or polymerized bovine hemoglobin (PolyBvHb; P-50 54.2 mmHg). Comparisons were made with the animals' hemodiluted blood with a non-O-2 carrying plasma expander with similar solution properties (Dextran-70). Systemic hemodynamics (arterial blood pressure and heart rate) and acid-base parameters were not correlated with microhemodynamics (arteriolar and venular diameter, red blood cell velocity, and flow). Microscopic measurements of PO2 and the O-2 equilibrium curves permitted analysis of O-2 release in precapillary and capillary vessels by red blood cells and plasma hemoglobin separately. No significant differences between the groups of animals with respect to arteriolar diameter, flow, or flow velocity were observed, but the functional capillary density was significantly higher in the MP4-treated animals (67%) compared with PolyBvHb-treated animals (37%; P < 0.05) or dextran-treated animals (53%). In the PolyBvHb-treated animals, predominant O-2 release (both red blood cells and plasma hemoglobin) occurred in precapillary vessels, whereas in MP4 animals most of the O-2 was released from both red blood cells and plasma hemoglobin in capillaries. Base excess correlated directly with capillary O-2 release but not systemic O-2 content or total O-2 release. Higher O-2 extraction of both red blood cell and plasma hemoglobin in capillaries represents a new mechanism of action of cell-free hemoglobin. High O-2 affinity appears to be an important property for cell-free hemoglobin solutions.