Summary
The concept that the p50 of a cell-free O2 carrier (“blood substitute”) should approximate that of human blood is rooted in the assumption that the p50 is an important determinant of O2 delivery. This assumption is based on antiquated measurements in subjects exposed to hypoxia, for whom a theory was developed that an increase in red cell 2,3-DPG shifts the oxygen equilibrium curve to the right (high p50, low O2 affinity), thereby providing “adaptation” to hypoxia. This concept has been carried over to efforts to pharmacologically raise the p50 of human red cells and to preserve 2,3-DPG concentration in banked blood. More recent measurements in high altitude natives demonstrate that such a right-shift is not critical to adaptation; in fact, a left shift is probably essential to maintain arterial saturation at extreme altitude. Furthermore, evidence of therapeutic benefit from increasing p50 in humans is scant. In the case of cell-free hemoglobin, the mechanisms of O2 transfer to tissue are completely different, such that unless p50 is significantly reduced, O2 oversupply will result, engaging autoregulatory mechanisms that leads to vasoconstriction. A second generation of O2 carriers has been designed with increased O2 affinity, and the suggestion is made that the optimal p50 for cell-free hemoglobin should be approximately that of the target tissue for oxygenation. In the case of highly metabolic tissue such as the myocardium or exercising skeletal muscle, this is in the range of 3–5 mmHg.
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© 2005 Springer-Verlag Tokyo
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Winslow, R.M. (2005). The Role of p50 in Tissue Oxygen Delivery by Cell-Free Oxygen Carriers. In: Kobayashi, K., Tsuchida, E., Horinouchi, H. (eds) Artificial Oxygen Carrier. Keio University International Symposia for Life Sciences and Medicine, vol 12. Springer, Tokyo. https://doi.org/10.1007/4-431-26651-8_4
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DOI: https://doi.org/10.1007/4-431-26651-8_4
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