Submitted on July 18, 2008
Revised on September 28, 2008
Accepted on September 29, 2008
ISOVOLEMIC EXCHANGE TRANSFUSION WITH INCREASING CONCENTRATIONS OF LOW OXYGEN AFFINITY HEMOGLOBIN SOLUTION LIMITS OXYGEN DELIVERY DUE TO VASOCONSTRICTION
Pedro Cabrales1*, Amy G. Tsai1, and Marcos Intaglietta1
1 University of California, San Diego
* To whom correspondence should be addressed. E-mail: pcabrales{at}ucsd.edu.
Oxygen (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% Hct) was induced by hemodilution with a plasma expander (dextran 70 kDa). After hemodilution, animals were randomly assigned to different exchange transfusion groups. Study groups were based on the concentration of PBH used, namely: PBH at 13gHb/dl [PBH13], PBH diluted to 8 or 4 gHb/dl in albumin solution at matching colloidal osmotic pressure (COP) [PBH8 and PBH4], and no PBH (only albumin solution) at matching COP [PBH0]. Measurement of systemic parameters, microvascular hemodynamics, capillary perfusion and intravascular and tissue O2 levels were 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 to 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.
