The influence of radial RBC distribution, blood velocity profiles, and glycocalyx on coupled NO/O2 transport.

The purpose of this investigation was to study the effect of the presence of red blood cells (RBCs) in the plasma layer near the arteriole wall on nitric oxide (NO) and oxygen (O2) transport. To this end, we extended a coupled NO and O2 diffusion-reaction model in the arteriole, developed by our group, to include the effect of the presence of RBCs in the plasma layer and the effect of convection. Two blood flow velocity profiles (plug and parabolic) were tested. The average hematocrit in the bloodstream was assumed to be constant in the central core and decreasing to zero in the boundary layer next to the endothelial surface layer. The effect of the presence or absence of RBCs near the endothelium was studied while varying the endothelial surface layer and boundary layer thickness. With RBCs present in the boundary layer, the model predicts that 1) NO decreases significantly in the endothelium and vascular wall; 2) there is a very small increase in endothelial and vascular wall Po2; 3) scavenging of NO by hemoglobin decreases with increasing thickness of the boundary layer; 4) the shape of the velocity profile influences both NO and Po2 gradients in the bloodstream; and 5) the presence of RBCs in the boundary layer near the endothelium has a much larger effect on NO than on O2 transport.

[1]  HirosukeKobayashi,et al.  Imaging of Oxygen Transfer Among Microvessels of Rat Cremaster Muscle , 2002 .

[2]  J. Stamler,et al.  Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[3]  R. Pittman,et al.  Influence of Microvascular Architecture on Oxygen Exchange in Skeletal Muscle , 1995, Microcirculation.

[4]  R. Johns,et al.  Determination of Km for oxygen of nitric oxide synthase isoforms. , 1996, The Journal of pharmacology and experimental therapeutics.

[5]  J. Lancaster,et al.  Simulation of the diffusion and reaction of endogenously produced nitric oxide. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[6]  C. Harteneck,et al.  Functional properties of a naturally occurring isoform of soluble guanylyl cyclase. , 1998, The Biochemical journal.

[7]  D. Jaron,et al.  Interactions between NO and O2 in the microcirculation: a mathematical analysis. , 2004, Microvascular research.

[8]  W. Kuschinsky,et al.  Measurements of the perivascular PO2 in the vicinity of the pial vessels of the cat , 1979, Pflügers Archiv.

[9]  J. H. Comroe,et al.  THE RATE OF UPTAKE OF CARBON MONOXIDE AND OF NITRIC OXIDE BY NORMAL HUMAN ERYTHROCYTES AND EXPERIMENTALLY PRODUCED SPHEROCYTES , 1958, The Journal of general physiology.

[10]  A. Popel,et al.  Erythrocyte consumption of nitric oxide in presence and absence of plasma-based hemoglobin. , 2002, American journal of physiology. Heart and circulatory physiology.

[11]  T. Lincoln,et al.  Regulation of intracellular Ca2+ levels in cultured vascular smooth muscle cells. Reduction of Ca2+ by atriopeptin and 8-bromo-cyclic GMP is mediated by cyclic GMP-dependent protein kinase. , 1989, The Journal of biological chemistry.

[12]  A. Popel,et al.  Rate of oxygen loss from arterioles is an order of magnitude higher than expected. , 1989, The American journal of physiology.

[13]  D. Buerk,et al.  Can we model nitric oxide biotransport? A survey of mathematical models for a simple diatomic molecule with surprisingly complex biological activities. , 2001, Annual review of biomedical engineering.

[14]  F. Murad,et al.  Cyclic guanosine monophosphate as a mediator of vasodilation. , 1986, The Journal of clinical investigation.

[15]  N Tateishi,et al.  Flow dynamics of erythrocytes in microvessels of isolated rabbit mesentery: cell-free layer and flow resistance. , 1994, Journal of biomechanics.

[16]  A. Copley,et al.  Nature of the endoendothelial layer as demonstrated by ruthenium red. , 1970, Experimental cell research.

[17]  J. Stamler,et al.  In vivo transfer of nitric oxide between a plasma protein-bound reservoir and low molecular weight thiols. , 1994, The Journal of clinical investigation.

[18]  A. Pries,et al.  Resistance to blood flow in microvessels in vivo. , 1994, Circulation research.

[19]  A. Popel,et al.  A two-phase model for flow of blood in narrow tubes with increased effective viscosity near the wall. , 2001, Biorheology.

[20]  D. Buerk,et al.  Microvascular and tissue oxygen gradients in the rat mesentery. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[21]  B. Duling,et al.  Capillary endothelial surface layer selectively reduces plasma solute distribution volume. , 2000, American journal of physiology. Heart and circulatory physiology.

[22]  Dov Jaron,et al.  Modeling the influence of superoxide dismutase on superoxide and nitric oxide interactions, including reversible inhibition of oxygen consumption. , 2003, Free radical biology & medicine.

[23]  Norio Ohshima,et al.  Simulation of intraluminal gas transport processes in the microcirculation , 1995, Annals of Biomedical Engineering.

[24]  J. Liao,et al.  Erythrocytes Possess an Intrinsic Barrier to Nitric Oxide Consumption* , 2000, The Journal of Biological Chemistry.

[25]  M. Singh,et al.  Optimum kinetic energy dissipation to maintain blood flow in glass capillaries: an analysis based on flow field determination by axial tomographic and image velocimetry techniques. , 1995, Journal of biomechanics.

[26]  J. Liao,et al.  Analysis of Nitric Oxide Consumption by Erythrocytes in Blood Vessels using a Distributed Multicellular Model , 2003, Annals of Biomedical Engineering.

[27]  Effects of shear stress on nitric oxide levels of human cerebral endothelial cells cultured in an artificial capillary system , 1999, Brain Research.

[28]  A. Popel,et al.  Estimating oxygen transport resistance of the microvascular wall. , 2000, American journal of physiology. Heart and circulatory physiology.

[29]  Marcos Intaglietta,et al.  Oxygen gradients in the microcirculation. , 2003, Physiological reviews.

[30]  T. Lagerlund,et al.  A mathematical simulation of oxygen delivery in rat peripheral nerve. , 1987, Microvascular research.

[31]  A. Pries,et al.  Corrections and Retraction , 2004 .

[32]  Q. Gibson,et al.  Conformation, co-operativity and ligand binding in human hemoglobin. , 1975, Journal of molecular biology.

[33]  Stephen C. Cowin,et al.  Mechanotransduction and flow across the endothelial glycocalyx , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[34]  D. Buerk,et al.  A SIMPLIFIED ALGORITHM FOR COMPUTING THE VARIATION IN OXYHEMOGLOBIN SATURATION WITH pH, PCO2, T AND DPG , 1986 .

[35]  Robin Fåhraeus.  Die Strömungsverhältnisse und die Verteilung der Blutzellen im Gefässystem , 2005, Klinische Wochenschrift.

[36]  Dov Jaron,et al.  Impact of the Fåhraeus Effect on NO and O2 Biotransport: A Computer Model , 2004, Microcirculation.

[37]  Modeling the regulation of oxygen consumption by nitric oxide. , 2003, Advances in experimental medicine and biology.

[38]  T. Lagerlund,et al.  Axial diffusion and Michaelis-Menten kinetics in oxygen delivery in rat peripheral nerve. , 1991, American Journal of Physiology.

[39]  Goldsmith,et al.  Robin Fåhraeus: evolution of his concepts in cardiovascular physiology. , 1989, The American journal of physiology.

[40]  T. Secomb,et al.  Analysis of oxygen exchange between arterioles and surrounding capillary-perfused tissue. , 1992, Journal of biomechanical engineering.

[41]  I. Megson,et al.  Diffusion of nitric oxide and scavenging by blood in the vasculature. , 1998, Biochimica et biophysica acta.

[42]  M. Marletta,et al.  Spectral and kinetic studies on the activation of soluble guanylate cyclase by nitric oxide. , 1996, Biochemistry.