title: Erythrocyte deformability is a nitric oxide-mediated factor in decreased capillary density during sepsis.
abstract: 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 (; micropipette aspiration), systemic NO production [plasma nitrite/nitrate (NO(x)) chemiluminescence], and NO accumulation in RBC [NO bound to hemoglobin (HbNO) detected by electron paramagnetic resonance spectroscopy]. In untreated CLP animals relative to sham, NO(x) increased 254% (P < 0.05), stopped flow capillaries increased 149% (P < 0.05), and decreased 12.7% (P < 0.05), with a subpopulation (5%) of RBC with deformabilities below the normal range. AG prevented increases in NO(x), accumulation of HbNO, and decreases in both 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.
authors.affiliation: Departments of Medical Biophysics, University of Western Ontario, London, Ontario N6A 5B8, Canada.
authors.forename: R M
authors.initials: RM
authors.lastname: Bateman
authors.forename: J E
authors.initials: JE
authors.lastname: Jagger
authors.forename: M D
authors.initials: MD
authors.lastname: Sharpe
authors.forename: M L
authors.initials: ML
authors.lastname: Ellsworth
authors.forename: S
authors.initials: S
authors.lastname: Mehta
authors.forename: C G
authors.initials: CG
authors.lastname: Ellis
mesh_terms: D000208:Acute Disease; D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D004907:Erythrocyte Deformability / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism; D006339:Heart Rate; D007958:Leukocyte Count; D008297:Male; D008833:Microcirculation / Q000503:physiopathology*; D018715:Microscopy, Video; D018482:Muscle, Skeletal / Q000098:blood supply*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D009573:Nitrites / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000503:physiopathology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D009566:Nitrates; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide