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Modulation of Perfusion and Oxygenation by Red Blood Cell Oxygen Affinity during Acute Anemia

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

Correspondence and requests for reprints should be addressed to Pedro Cabrales, Ph.D., La Jolla Bioengineering Institute, 505 Coast Boulevard South, Suite #405, La Jolla, CA 92037. E-mail: pcabrales{at}ucsd.edu

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 (partial pressure of O₂ at 50% Hb saturation) were modified to 10, 25, 45, and 50 mm Hg (normal P50 is 32 mm Hg). Allosteric effectors also decreased the Hill coefficient. Anemic condition was induced by isovolemic hemodilution exchanges using 6% dextran 70 kD 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 mm Hg 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. Erythrocytes 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.

Key Words: microcirculation • hemodilution • functional capillary density • tissue oxygen • hemoglobin allosteric effectors

CLINICAL RELEVANCE This study shows that the criterion for an optimal blood Hb-oxygen affinity for exchange transfused blood is not unique and requires differentiating between microvascular function and tissue oxygen tension.