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Am J Physiol Heart Circ Physiol 280: H2848-H2856, 2001;
0363-6135/01 $5.00
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Vol. 280, Issue 6, H2848-H2856, June 2001

Erythrocyte deformability is a nitric oxide-mediated factor in decreased capillary density during sepsis

Ryon M. Bateman1, Justin E. Jagger1, Michael D. Sharpe2, Mary L. Ellsworth4, Sanjay Mehta3, and Christopher G. Ellis1

1 Departments of Medical Biophysics, 2 Anaesthesia, and 3 Respirology, University of Western Ontario, London, Ontario N6A 5B8, Canada; and 4 Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, Missouri 63104

Erythrocyte deformability has been recognized as a determinant of microvascular perfusion. Because nitric oxide (NO) is implicated in the modulation of red blood cell (RBC) deformability and NO levels increase during sepsis, we tested the hypothesis that a NO-mediated decrease in RBC deformability contributes to decreased functional capillary density (CD) in remote organs. With the use of a peritonitis model of sepsis in the rat [cecal ligation and perforation (CLP)] and aminoguanidine (AG) to prevent increases in NO, we measured CD in skeletal muscle (intravital microscopy), mean erythrocyte membrane deformability (<A><AC>&dgr;</AC><AC>&cjs1171;</AC></A>; micropipette aspiration), systemic NO production [plasma nitrite/nitrate (NOx) chemiluminescence], and NO accumulation in RBC [NO bound to hemoglobin (HbNO) detected by electron paramagnetic resonance spectroscopy]. In untreated CLP animals relative to sham, NOx increased 254% (P < 0.05), stopped flow capillaries increased 149% (P < 0.05), and <A><AC>&dgr;</AC><AC>&cjs1171;</AC></A> decreased 12.7% (P < 0.05), with a subpopulation (5%) of RBC with deformabilities below the normal range. AG prevented increases in NOx, accumulation of HbNO, and decreases in both <A><AC>&dgr;</AC><AC>&cjs1171;</AC></A> and functional CD. We found no evidence of leukocyte plugging postcapillary venules. Our findings suggest that decreased functional CD during sepsis resulted from a NO-mediated decrease in erythrocyte deformability.

microcirculation; abnormalities; septicemia; functional capillary density


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