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Published ahead of print on September 20, 2007, doi:10.1165/rcmb.2007-0292OC

Am. J. Respir. Cell Mol. Biol., Volume 38, Number 3, March 2008, 354-361

A more recent version of this article appeared on March 1, 2008
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Submitted on July 30, 2007
Revised on September 19, 2007

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

Pedro Cabrales1*, Amy G Tsai2, and Marcos Intaglietta3

1 La Jolla Bioengineering Institute, La Jolla, CA, USA, 2 La Jolla Bioengineering Institute, La Jolla, CA, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA, 3 Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA

* To whom correspondence should be addressed. 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 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. 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.






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Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2007 American Thoracic Society.