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Am J Physiol Heart Circ Physiol 295: H2212-H2218, 2008. First published October 3, 2008; doi:10.1152/ajpheart.00751.2008
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Isovolemic exchange transfusion with increasing concentrations of low oxygen affinity hemoglobin solution limits oxygen delivery due to vasoconstriction

Pedro Cabrales,1 Amy G. Tsai,1,2 and Marcos Intaglietta2

1La Jolla Bioengineering Institute and 2Department of Bioengineering, University of California, San Diego, La Jolla, California

Submitted 18 July 2008 ; accepted in final form 29 September 2008

O2-carrying fluids based on hemoglobin (Hb) are in various stages of clinical trials to determine their suitability as O2-carrying plasma expanders. Polymerized Hb solutions are characterized by their vasoactivity, low O2 affinity, oncotic effect, prolonged shelf life, and stability. Physiological responses to facilitated O2 transport after exchange transfusion with polymerized bovine Hb (PBH) were studied in the hamster window chamber model during acute moderate anemia to determine how PBH affects microvascular perfusion and tissue oxygenation. The anemic state [29% hematocrit (Hct)] was induced by hemodilution with a plasma expander (70 kDa dextran). After hemodilution, animals were randomly assigned to different exchange transfusion groups. Study groups were based on the concentration of PBH used, namely: PBH at 13 g Hb/dl [PBH13], PBH diluted to 8 (PBH8) or 4 (PBH4) g Hb/dl in albumin solution at matching colloidal osmotic pressure (COP), and no PBH (only albumin solution) at matching COP (PBH0). Measurement of systemic parameters, microvascular hemodynamics, capillary perfusion, and intravascular and tissue O2 levels was performed at 18% Hct. Restitution of O2-carrying capacity with PBH13 increased arterial pressure and triggered vasoconstriction, low perfusion, and high peripheral resistance. PBH4 and PBH0 exhibited lower arterial pressures compared with PBH13. Exchange transfused animals with PBH8 and PBH4 better maintained perfusion and functional capillary density than PBH13. Blood gas parameters and acid-base balance were recovered proportional to microvascular perfusion. Arterial O2 tensions were improved with PBH4 and PBH8 by preventing O2 precapillary release and increasing O2 reserve. Further studies to establish PBH optimal dosage, efficacy, safety, and its effect on outcome are indicated before Hb-based O2-carrying blood substitutes are implemented in routine practice.

microcirculation; red blood cells; hemodilution; functional capillary density; hemoglobin oxygen affinity; tissue oxygen


Address for reprint requests and other correspondence: P. Cabrales, La Jolla Bioengineering Institute, 505 Coast Boulevard South Suite #405, La Jolla, CA 92037 (e-mail: pcabrales{at}ucsd.edu)






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