Resistance to blood flow in microvessels in vivo.
TL;DR: A new approach for calculating the contribution of blood rheology to microvascular flow resistance is presented, and unexpectedly high flow resistance in small microvessels may be related to interactions between blood components and the inner vessel surface that do not occur in smooth-walled tubes.
Abstract: Resistance to blood flow through peripheral vascular beds strongly influences cardiovascular function and transport to tissue. For a given vascular architecture, flow resistance is determined by the rheological behavior of blood flowing through microvessels. A new approach for calculating the contribution of blood rheology to microvascular flow resistance is presented. Morphology (diameter and length), flow velocity, hematocrit, and topological position were determined for all vessel segments (up to 913) of terminal microcirculatory networks in the rat mesentery by intravital microscopy. Flow velocity and hematocrit were also predicted from mathematical flow simulations, in which the assumed dependence of flow resistance on diameter, hematocrit, and shear rate was optimized to minimize the deviation between measured and predicted values. For microvessels with diameters below approximately 40 microns, the resulting flow resistances are markedly higher and show a stronger dependence on hematocrit than previously estimated from measurements of blood flow in narrow glass tubes. For example, flow resistance in 10-microns microvessels at normal hematocrit is found to exceed that of a corresponding glass tube by a factor of approximately 4. In separate experiments, flow resistance of microvascular networks was estimated from direct measurements of total pressure drop and volume flow, at systemic hematocrits intentionally varied from 0.08 to 0.68. The results agree closely with predictions based on the above-optimized resistance but not with predictions based on glass-tube data. The unexpectedly high flow resistance in small microvessels may be related to interactions between blood components and the inner vessel surface that do not occur in smooth-walled tubes.
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TL;DR: The mechanical and biochemical properties of the EGL and the latest studies on the interactions of this layer with red and white blood cells are examined, including its deformation owing to fluid shear stress, its penetration by leukocyte microvilli, and its restorative response after the passage of a white cell in a tightly fitting capillary.
Abstract: Over the past decade, since it was first observed in vivo, there has been an explosion in interest in the thin (∼500 nm), gel-like endothelial glycocalyx layer (EGL) that coats the luminal surface of blood vessels. In this review, we examine the mechanical and biochemical properties of the EGL and the latest studies on the interactions of this layer with red and white blood cells. This includes its deformation owing to fluid shear stress, its penetration by leukocyte microvilli, and its restorative response after the passage of a white cell in a tightly fitting capillary. We also examine recently discovered functions of the EGL in modulating the oncotic forces that regulate the exchange of water in microvessels and the role of the EGL in transducing fluid shear stress into the intracellular cytoskeleton of endothelial cells, in the initiation of intracellular signaling, and in the inflammatory response.
1,005 citations
TL;DR: Investigations in vivo have indicated the presence of a much thicker endothelial surface layer (ESL) that restricts the flow of plasma and can exclude red blood cells and some macromolecular solutes.
Abstract: The endothelial lining of blood vessels presents a large surface area for exchange of materials between blood and tissues, and is critically involved in many other processes such as regulation of blood flow, inflammatory responses and blood coagulation. It has long been known that the luminal surface of the endothelium is lined with a glycocalyx, a layer of membrane-bound macromolecules which has been determined by electron microscopy to be several tens of nanometers thick. However, investigations in vivo have indicated the presence of a much thicker endothelial surface layer (ESL), with an estimated thickness ranging from 0.5 µm to over 1 µm, that restricts the flow of plasma and can exclude red blood cells and some macromolecular solutes. The evidence for the existence of the ESL, hypotheses about its composition and biophysical properties, its relevance to physiological processes, and its possible clinical implications are considered in this review.
859 citations
TL;DR: Short-term and long-term regulation of the microvasculature is discussed; the modes of regulation include metabolic, myogenic and shear-stress-dependent mechanisms as well as vascular adaptation such as angiogenesis and vascular remodeling.
Abstract: Major experimental and theoretical studies on microcirculation and hemorheology are reviewed with the focus on mechanics of blood flow and the vascular wall. Flow of the blood formed elements (red blood cells (RBCs), white blood cells or leukocytes (WBCs) and platelets) in individual arterioles, capillaries and venules, and in microvascular networks is discussed. Mechanical and rheological properties of the formed elements and their interactions with the vascular wall are reviewed. Short-term and long-term regulation of the microvasculature is discussed; the modes of regulation include metabolic, myogenic and shear-stress-dependent mechanisms as well as vascular adaptation such as angiogenesis and vascular remodeling.
685 citations
TL;DR: It is concluded that the wall of skeletal muscle capillaries is decorated with a 0.4- to 0.5-microns-thick endothelial surface coat, which may represent the true active interface between blood and the capillary wall.
Abstract: A thick endothelial surface coat consisting of the glycocalyx and associated plasma proteins has been hypothesized to reduce functional capillary volume available for flowing plasma macromolecules and blood cells. The purpose of this study was to compare anatomic and functional capillary diameters available for macromolecules, RBCs, and WBCs in hamster cremaster muscle capillaries. Bright-field and fluorescence microscopy provided similar estimates (mean +/- SE) of the anatomic capillary diameter: 5.1 +/- 0.1 microns (bright field, 39 capillaries in 10 animals) and 5.1 +/- 0.2 microns (membrane dye PKH26, 18 capillaries in 2 animals). Estimates of functional diameters were obtained by measuring the width of RBCs and WBCs and the intracapillary distribution of systemically injected fluorescein isothiocyanate (FITC)-dextran 70. WBCs (5.1 +/- 0.2 microns) fully occupied the anatomic capillary cross section. In contrast, the widths of RBCs (3.9 +/- 0.2 microns, 21 capillaries in 8 animals) and FITC-dextran (4.3 +/- 0.2 microns, 21 capillaries in 8 animals) were significantly smaller than the anatomic capillary diameter. Continuous (1- to 5-minute) excitation of fluorochromes in the capillary lumen (light-dye treatment) increased the width of RBCs passing the treated site from 3.6 +/- 0.3 to 4.4 +/- 0.3 microns (6 capillaries in 4 animals) and the width of the FITC-dextran column from 4.1 +/- 0.2 to 4.6 +/- 0.3 microns (10 capillaries in 7 animals). Furthermore, light-dye treatment increased capillary tube hematocrit by 60% in 40-microns-long capillary segments compared with untreated sites in the same capillaries. It is concluded that the wall of skeletal muscle capillaries is decorated with a 0.4- to 0.5-microns-thick endothelial surface coat, which may represent the true active interface between blood and the capillary wall.
590 citations
TL;DR: It is shown that blood flow and red blood cell heterogeneity play major roles in the development of such colonies, even when the red blood cells are flowing through the vasculature of normal, healthy tissue.
437 citations
Cites background from "Resistance to blood flow in microve..."
...Keywords: Tumour growth; Blood flow; Heterogeneity; Cellular automaton...
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...However, Pries et al. managed to fit the following explicit expression for the viscosity as a function of R and H to detailed experimental data (Pries et al., 1994): mrel ¼ 1þ ðm 0:45 1Þ ð1 HÞC 1 ð1 0:45ÞC 1 2R 2R 1:1 2" # 2R 2R 1:1 2 ; m 0:45 ¼ 6e 0:17R þ 3:2 2:44e 0:06ð2RÞ 0:645 ; C ¼ ð0:8þ e…...
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...This behaviour persists until the vessel radius is of the order of 15–20 mm: The viscosity then reaches a minimum and, thereafter, increases if R is similar in magnitude to the radius of a red blood cell (Pries et al., 1994)....
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...Firstly, blood is a complex suspension of different elements, with a complex rheology (Pries et al., 1994)....
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...(4) vi ’Qi=pR2i is the average flow velocity on a section orthogonal to the axis of the vessel, a is a phenomenological parameter which accounts for strength of the non-symmetry of the haematocrit distribution at bifurcations, and THR is the value of the ratio between the velocities of the branches…...
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References
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TL;DR: Objections have been made from a theoretical point of view that the results of investigations of the viscosity of the blood in comparatively wide capillary tubes probably do not apply to the conditions in the narrower parts of the vascular system, whereby these authors especially seem to have had the true capillaries in view.
Abstract: Nearly one hundred years have passed since the French physician Poiseuille (1) took up for consideration the important problem of the resistance of the bloodstream in the narrow parts of the vascular system. As experimental difficulties arose with blood, his fundamental investigations were contied to experiments with water and different fluids in glass capillaries w He found, as is well known, that the time of efflux of a given volume of fluid is directly as the length of the tube, inversely as the difference of pressure at the two ends and inversely as the fourth power of the diameter. During the following time the law of Poiseuille seems to have been generally accepted with regard to the blood also and the results of the first experimental studies by Ewald (2) and Benno Lewy (3) were, like those of many re-examinations, in accordance with the law in question. The now prevailing opinion is that the blood behaves as a real fluid in the vascular system with regard to its viscosity (see the survey by Neuschlosz, 4). Against this opinion, however, objections have been made from a theoretical point of view. Von Kries (5) and Hiirthle (6) have pointed out that the results of investigations of the viscosity of the blood in comparatively wide capillary tubes probably do not apply to the conditions in the narrower parts of the vascular system, whereby these authors especially seem to have had the true capillaries in view. As far as we know, the only statement in the literature regarding the viscosity of the blood being altered in narrow capillary tubes is found in the paper of Denning and Watson (7) In the narrowest capillary employed in their researches, namely, one of a diameter of 0.3 mm., they observed increased values. This result is, however, certainly erroneous, for reasons that will be given below. It is true that the viscosity of the blood has been earlier investigated in capillary tubes, where a divergence from the law of Poiseuille-corresponding to our own results-ought to appear. Thus Hess (8) has examined the viscosity of the same blood in capillaries of a diameter of 0.239 and 0.126 mm. respectively under the same conditions. A calculation on the basis
1,154 citations
TL;DR: The present study provides a comprehensive data base for the description of relative apparent blood viscosity as a function of tube diameter and hematocrit and presents empirical fitting equations predicting relative apparentBlood viscosities from tube diameter, as well as new experimental data obtained in a capillary viscometer.
Abstract: Since the original publications by Martini et al. (Dtsch. Arch. Klin. Med. 169: 212–222, 1930) and Fahraeus and Lindqvist (Am. J. Physiol. 96: 562–568, 1931), it has been known that the relative ap...
680 citations
TL;DR: The low capillary hematocrits found in mesenteric microcirculatory networks as well as their heterogeneity can be explained on the basis of the Fahraeus effect and phase-separation phenomena.
Abstract: A theoretical model has been developed to simulate blood flow through large microcirculatory networks. The model takes into account the dependence of apparent viscosity of blood on vessel diameter and hematocrit (the Fahraeus-Lindqvist effect), the reduction of intravascular hematocrit relative to the inflow hematocrit of a vessel (the Fahraeus effect), and the disproportionate distribution of red blood cells and plasma at arteriolar bifurcations (phase separation). The model was used to simulate flow in three microvascular networks in the rat mesentery with 436,583, and 913 vessel segments, respectively, using experimental data (length, diameter, and topological organization) obtained from the same networks. Measurements of hematocrit and flow direction in all vessel segments of these networks tested the validity of model results. These tests demonstrate that the prediction of parameters for individual vessel segments in large networks exhibits a high degree of uncertainty; for example, the squared coefficient of correlation between predicted and measured hematocrit of single vessel segments ranges only between 0.15 and 0.33. In contrast, the simulation of integrated characteristics of the network hemodynamics, such as the mean segment hematocrit or the distribution of blood flow velocities, is very precise. In addition, the following conclusions were derived from the comparison of predicted and measured values: 1) The low capillary hematocrits found in mesenteric microcirculatory networks as well as their heterogeneity can be explained on the basis of the Fahraeus effect and phase-separation phenomena. 2) The apparent viscosity of blood in vessels of the investigated tissue with diameters less than 15 microns is substantially higher than expected compared with measurements in glass tubes with the same diameter.
538 citations
TL;DR: An apparent maintenance of Poiseuille's law is attributed to the opposing processes of hematocrit reduction and decreasing shear rate as blood is dispersed in successive arteriolar segments, and the converse action of these processes in the venous confluences which lessen the extent of network variations in apparent viscosity.
Abstract: In vivo studies of the rheological behavior of blood in the microcirculation were conducted by direct in situ measurements in cat mesentery. Upstream to downstream pressure drops were measured in unbranched arterioles, capillaries, and venules, with diameters from 7 to 58 micrometer. Simultaneous measurements of red cell velocity and vessel geometry facilitated computation of bulk velocity, pressure gradient, apparent viscosity, wall shear stress, and resistance. Arteriovenous distributions of these parameters revealed the following. Maximum pressure gradient (0.015 cm H20/micrometer) occurs in the true capillaries (7 micrometer in diameter); intravascular wall shear stress averaged 47.1 dynes/cm2 in arterioles and 29.0 dynes/cm2 in venules. Extreme values as great as 200 dynes/cm2 were observed in a few shunting arterioles. Apparent viscosity averaged 3.59 cP in arterioles, 5.15 cP in venules, and 4.22 cP overall. Intravascular resistance per unit length of microvessel varied with luminal diameter as a p...
398 citations
TL;DR: Conservation of red cell flux throughout the mesenteric network was partially demonstrated upon applying previously established in vitro relationships between discharge and tube hematocrits, the resulting disparity being attributed to the rheological behavior of blood and possible A-V shunting of red cells.
381 citations