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Am J Physiol Heart Circ Physiol 288: H2897-H2903, 2005. First published January 28, 2005; doi:10.1152/ajpheart.01184.2004
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Oxygen release from low and normal P50 Hb vesicles in transiently occluded arterioles of the hamster window model

Hiromi Sakai,1 Pedro Cabrales,2,3 Amy G. Tsai,2,3 Eishun Tsuchida,1 and Marcos Intaglietta2,3

1Advanced Research Institute for Science and Engineering, Waseda University, Tokyo, Japan; and 2Department of Bioengineering, University of California-San Diego, and 3La Jolla Bioengineering Institute, La Jolla, California

Submitted 27 November 2004 ; accepted in final form 24 January 2005

A phospholipid vesicle encapsulating Hb [Hb vesicle (HbV)] has been developed as a transfusion alternative. One characteristic of HbV is that the O2 affinity [PO2 at which Hb is 50% saturated (P50)] of Hb can be easily regulated by the amount of the coencapsulated allosteric effector pyridoxal 5'-phosphate. In this study, we prepared two HbVs with different P50s (8 and 29 mmHg, termed HbV8 and HbV29, respectively) and observed their O2-releasing behavior from an occluded arteriole in a hamster skinfold window model. Conscious hamsters received HbV8 or HbV29 at a dose rate of 7 ml/kg. In the microscopic view, an arteriole (diameter: 53.0 ± 6.6 µm) was occluded transcutaneously by a glass pipette on a manipulator, and the reduction of the intra-arteriolar PO2 100 µm down from the occlusion was measured by the phosphorescence quenching of preinfused Pd-porphyrin. The baseline arteriolar PO2 (50–52 mmHg) decreased to about 5 mmHg for all the groups. Occlusion after HbV8 infusion showed a slightly slower rate of PO2 reduction compared with that after HbV29 infusion. The arteriolar O2 content was calculated at each reducing PO2 in combination with the O2 equilibrium curves of HbVs, and it was clarified that HbV8 showed a significantly slower rate of O2 release compared with HbV29 and was a primary source of O2 (maximum fraction, 0.55) overwhelming red blood cells when the PO2 was reduced (e.g., <10 mmHg) despite a small dosage of HbV. This result supports the possible utilization of Hb-based O2 carriers with lower P50 for oxygenation of ischemic tissues.

blood substitutes; artificial red blood cells; occlusion; microhemodynamics; liposome



Address for reprint requests and other correspondence: E. Tsuchida, Advanced Research Institute for Science and Engineering, Waseda Univ., Tokyo 169-8555, Japan (E-mail: eishun{at}waseda.jp)




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