Abstract
Responses to exchange transfusion using red blood cells (RBCs) with modified hemoglobin (Hb) oxygen (O2) affinity were studied in the hamster window chamber model during acute anemia to determine its role on microvascular perfusion and tissue oxygenation. Allosteric effectors were introduced in the RBCs by electroporation. Inositol hexaphosphate (IHP) and 5‐hydroxymethyl‐2‐furfural (5HMF) were used to decrease and increase Hb‐O2 affinity. In vitro P50s were modified to 10, 25, 45 and 50 mmHg, normal P50 is 32 mmHg. Allosteric effectors also decreased the Hill coefficient. Anemic condition was induced by isovolemic hemodilution exchanges using 6% dextran 70 kDa to 18% hematocrit (Hct). Modified RBCs (at 18% Hct in 5% albumin solution) were infused by exchange transfusion of 35% of blood volume. Systemic parameters, microvascular perfusion, capillary perfusion (functional capillary density, FCD) and microvascular pO2 levels were measured. RBCs with P50 of 45 mmHg increased tissue pO2 and decreased O2 delivery (DO2) and extraction (VO2) and RBCs with P50 of 60 mmHg reduced FCD, microvascular flow, tissue pO2, DO2 and VO2. RBCs with increased Hb‐O2 affinity maintained hemodynamic conditions, DO2 and decreased tissue pO2. This study shows that in an anemic condition maximal tissue pO2 does not correspond to maximal DO2 and VO2. Supported by NIH BRP R24‐HL64395 and grants R01‐HL62354, R01‐HL62318 and R01‐HL76182.
Published Version
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