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1 Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA
2 Sangart Inc, San Diego, CA, USA
3 Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA; Sangart Inc, San Diego, CA, USA
* To whom correspondence should be addressed. E-mail: agtsai{at}ucsd.edu.
To assess O2 delivery to tissue by a new surface-modified, polyethyleneglycol-conjugated human hemoglobin (MP4, P50 5.4 mmHg), we studied microcirculatory hemodynamics and O2 release in Golden Syrian Hamsters hemodiluted with MP4 or polymerized bovine hemoglobin (PolyBvHb, P50 54.2 mmHg). Comparisons were made with animals hemodiluted with a non-O2 carrying plasma expander with similar solution properties (Dextran 70 kDa). 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 oxygen equilibrium curves permitted analysis of O2 release in precapillary and capillary vessels by red 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 functional capillary density was significantly higher in the MP4 animals (67%) compared to PolyBvHb animals (37%) (P < 0.05) or Dextran animals (53%). In the PolyBvHb animals, predominant O2 release (both red cell and plasma Hb) occurred in precapillary vessels, while in MP4 animals most of the O2 was released from both red cells and plasma Hb in capillaries. Base excess correlated directly with capillary O2 release, but not systemic O2 content or total O2 release. Higher O2 extraction of both red cell and plasma Hb in capillaries represents a new mechanism of action of cell-free hemoglobin. High oxygen affinity appears to be an important property for cell-free hemoglobin solutions.
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