| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Physiology, Freie Universität Berlin, D-14195 Berlin, Germany; and 2 Department of Physiology, University of Arizona, Tucson, Arizona 85724
 |
ABSTRACT |
|---|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
Observations of blood flow in microvascular networks have shown that the resistance to blood flow is about twice that expected from studies using narrow glass tubes. The goal of the present study was to test the hypothesis that a macromolecular layer (glycocalyx) lining the endothelial surface contributes to blood flow resistance. Changes in flow resistance in microvascular networks of the rat mesentery were observed with microinfusion of enzymes targeted at oligosaccharide side chains in the glycocalyx. Infusion of heparinase resulted in a sustained decrease in estimated flow resistance of 14-21%, hydrodynamically equivalent to a uniform increase of vessel diameter by ~1 µm. Infusion of neuraminidase led to accumulation of platelets on the endothelium and doubled flow resistance. Additional experiments in untreated vascular networks in which microvascular blood flow was reduced by partial microocclusion of the feeding arteriole showed a substantial increase of flow resistance at low flow rates (average capillary flow velocities < 100 diameters/s). These observations indicate that the glycocalyx has significant hemodynamic relevance that may increase at low flow rates, possibly because of a shear-dependent variation in glycocalyx thickness.
rheology; microvascular networks; shear rate; glycocalyx
| |
INTRODUCTION |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
SEVERAL physiologically important functions of microvessels are known to be affected by the surface characteristics of microvascular endothelium. These characteristics are determined by a macromolecular lining, referred to as the glycocalyx, that includes both molecules directly bound to the plasma membrane of the endothelial cells and components adsorbed from the blood plasma. The glycocalyx has been shown to influence several aspects of vascular function, including the metabolic status of endothelial cells (31), endothelial permeability to water and solutes (32), leukocyte adhesion and emigration (11), and microvascular hematocrit (6).
The effect of the glycocalyx on capillary hematocrit has been attributed to a restriction of the luminal volume available for flow of plasma and red blood cells (6, 7). Such a restriction could also alter vascular flow resistance. Observations of blood flow in microvascular networks and direct measurements of pressure drop and volume flow rates in vivo have shown that the resistance to blood flow is about twice as large as expected from tube flow studies (12, 13, 23). A number of mechanisms that could increase flow resistance in vivo compared with that of glass tubes with corresponding diameters have been proposed: 1) irregularity of vessel lumen, 2) entrance effects at vascular branch points, 3) flow properties of white blood cells, and 4) restriction of flow by a macromolecular lining on the endothelial surface.
Available studies (4, 20, 28, 34, 35) suggest that the first three effects are not sufficient to quantitatively explain the observed high blood flow resistance in vivo. Therefore, the aim of the present study was to examine the effect of the glycocalyx on flow resistance by measuring changes in resistance after microinfusion of enzymes cleaving components of glycocalyx oligosaccharide side chains. Because changes of surface shear forces caused by blood flow might affect glycocalyx properties, the effect of blood flow rate on flow resistance was also examined. The rat mesentery preparation used is well suited for these studies, because its microvessels do not exhibit spontaneous changes of vascular tone that might influence flow resistance during the experiments.
| |
MATERIALS AND METHODS |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
Intravital microscopy.
Experiments were conducted in the microvasculature of the rat mesentery
with intravital microscopy after approval of the procedures used by
university and governmental committees on animal care. Details of the
animal preparation and the setup used for intravital microscopy have
been described elsewhere (22). Male Wistar rats (body wt 300-450
g) were prepared for intravital microscopy of the mesenteric
microcirculation after premedication (atropine 0.1 mg/kg im and
pentobarbital sodium 20 mg/kg im); anesthesia (ketamine 100 mg/kg im);
cannulation of trachea, jugular vein, and carotid artery; and abdominal
midline incision. During the experiments, which lasted for up to 2 h,
the level of anesthesia and fluid balance were maintained by infusion
of physiological saline (24 ml · kg
1 · h1
iv) containing 0.3 mg/ml pentobarbital sodium. Heart rate and arterial
blood pressure (range 105-140 mmHg) were continuously monitored
via the catheter in the carotid artery. The animals were transferred to
a special stage mounted on an intravital microscope. The small bowel
was exteriorized, and fat-free portions of the mesentery were selected
for investigation with a ×25, NA 0.6 saltwater immersion
objective (Leitz). In this preparation, vessels generally do not
exhibit any spontaneous smooth muscle tone. As a precaution to prevent
the development of tone and thus temporal variation of flow resistance
during the measurement period, papaverine
(104 M) was continuously
superfused. Two series of experiments using different approaches were
performed.
Bifurcation experiments. In a series of 28 experiments, changes in the flows in the two daughter branches of a bifurcating feeding arteriole were used to analyze the effect of enzymes and of buffer solutions with altered osmolarity microinfused into one daughter vessel and its dependent vessel network (Fig. 1). Changes of systemic hemodynamic conditions, including blood pressure, upstream arterial vessel tone, and changes of blood rheological properties, can be assumed to have equivalent effects on the flows in both treated and untreated daughter vessels. Therefore, observed changes in the flow velocity ratio between these vessels reflect changes in the resistance of the treated vessel and its dependent network, independent of any systemic effects of the treatment.
|
R) in the treated network, fed
by the microinfused daughter branch, was estimated from the changes in
the flow velocity ratio between the two branches. Vessel diameters
remained constant during the experiment as ascertained by occasional
measurements. Flow velocity (V) in
each branch is inversely related to the flow resistance
(R) in that branch and its
downstream ramifications. Therefore, the resistance of the network fed
by the daughter branch to which the microinfusion was applied
(RT) is
related, both before and after enzyme treatment, to the resistance of
the untreated control network
(RU)
by
|
(1) |
R in the
treated network can be expressed as
|
(2) |
Network experiments. To estimate resistance changes on heparinase treatment, 12 experiments were performed with this enzyme using a different technique. The flow resistance of microvascular networks in the rat mesentery was estimated by measuring arteriolovenular pressure drop and volume flow rate before and after local microinfusion of heparinase (Fig. 1). The networks investigated were fed by arterioles with inner diameters of ~30 µm and drained by venules of ~45-µm diameter. As in previous studies in the same preparation, such networks consist of ~450 individual vessel segments (21). Intravascular pressures in the feeding arteriole and the draining venule were measured according to the servo-nulling technique using a micropipette with a tip diameter of ~1 µm connected to a micropressure measuring system (model 5, IPM; Ref. 9).
After an initial measurement of venular pressure, the micropipette was impaled into the main feeding arteriole where it remained during the experimental period (up to 60 min). For each determination of network flow resistance, arteriolar pressure was monitored and the image of the vessel, obtained with a charge-coupled device camera (MX, AIS), was recorded on videotape for ~30 s using asynchronous flash illumination (11360-1, Chadwick-Helmuth). The experiment was completed by a measurement of venular pressure to test the stability of arteriolovenular pressure gradient and a measurement of zero pressure (in the superfusing solution) to test the stability of micropressure recordings. The venular pressures at the beginning and the end of the experiment averaged 13.4 ± 1.8 and 11.8 ± 2.1 mmHg, respectively. A linear interpolation of the two venular pressures for each experiment was used in the calculations of flow resistance at a given time during the experiment. Because the micropipette remained in place before and after heparinase microinfusion, observed changes in resistance could not have resulted from perturbations of pressure caused by micropipette insertion. Furthermore, such perturbations were probably small, because the pipette tip was much smaller than the impaled vessels. The video recordings were analyzed off-line to determine arteriolar flow velocity and vessel diameter using a digital image analysis system (23). The spatial correlation analysis of recordings obtained with asynchronous illumination allowed measurements of blood flow velocities up to ~40 mm/s. A previously established method (23) based on parametric descriptions of the Fahraeus effect and a spatial averaging model was used to convert the obtained centerline velocities into mean blood flow velocities. A digital image analysis system was used to measure vessel diameters interactively (16). The precision of this method as determined by repeated measurements ranges between 0.5 and 1 µm (20). Because arteriolar diameters exhibited no detectable variations during the experiments or after enzyme treatment, relative changes of network flow resistance were calculated from relative changes in pressure drop and arteriolar flow velocity. In 9 of 12 experiments of this series, the network was perfused for 5 or 10 min with heparinase in the vehicle solution described above via a micropipette impaled into the feeding arteriole. Velocity data and arteriolar pressure readings were sampled several times in the control state, as well as repeatedly for ~30 min after the end of the heparinase infusion, to allow estimations of network flow resistance. In three additional experiments of this series, the influence of variation of flow rate on network flow resistance was analyzed without any previous enzyme treatment. A graded reduction of blood flow in the microvessel networks was achieved by partial occlusion of the feeding arteriole with a blunted micropipette proximal to the point of pressure measurement. Graded flow reduction was repeated after varying the systemic hematocrit (HS) to different levels between 0.52 and 0.07 by isovolemic or hypervolemic exchange of blood with homologous red blood cells, plasma, or hydroxyethyl starch solution (100 g/l, mol wt 200,000/0.5 in physiological saline where 0.5 indicates the degree of substitution in the starch molecule; Fresenius) according to a procedure described previously (23). Because reduction of flow rate in the feeding arteriole by partial occlusion may lead to upstream phase separation and thereby decrease hematocrit and flow resistance in the network studied, the hematocrit in the feeding arteriole was continuously measured by off-line videodensitometric analysis (17, 22). The image of the vessel was recorded on videotape using monochromatic illumination (wavelength 448 nm). An in vivo calibration for each vessel was established, assuming that the discharge hematocrit in the arteriole (H) in the unoccluded state was equal to HS. Experimental values of optical density (OD) measured in the unoccluded vessel during variation of HS were used to determine the parameters a and b of the linear regression
|
(3) |
![<IT>R</IT> = <IT>A</IT> + <IT>B</IT> ⋅ [(1 − H<SUB>S</SUB> )<SUP><IT>C</IT></SUP> −1]](/content/vol273/issue5/fulltext/H2272/img004.gif)
|
(4) |
![<IT>R</IT><SUB><IT>C</IT></SUB> = <IT>R</IT><SUB>0</SUB> ⋅ <FR><NU><IT>A</IT> + <IT>B</IT> ⋅ [(1 − H<SUB>S</SUB>)<SUP><IT>C</IT></SUP> − 1]</NU><DE><IT>A</IT> + B ⋅ [(1 − H)<SUP><IT>C</IT></SUP> − 1]</DE></FR>](/content/vol273/issue5/fulltext/H2272/img005.gif)
|
(5) |
Statistics. Mean values were compared by a one-way analysis of variance procedure using Tukey-B correction for post hoc multiple comparisons. Significance is indicated at the P < 0.05 level.
| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
Table 1 gives averaged morphological and hemodynamic values for arterioles of both bifurcation and network experiments. In the bifurcation experiments, vessel diameters were measured at the site of velocity measurement. In these experiments, no statistically significant difference between the parameters for the two branches (infused and untreated) of the observed bifurcation was observed.
|
Figure 2 shows results of heparinase infusion in a typical bifurcation experiment. Flow velocity in the untreated branch exhibited no substantial change during the experimental period, whereas flow velocity in the treated branch increased substantially after the enzyme infusion. This indicates a reduction of flow resistance in the microvascular network fed by the treated branch. Average changes of flow resistance with time after vehicle infusion and heparinase infusion in the bifurcation experiments are shown in Fig. 3. Postinfusion values of flow resistance change are slightly elevated after infusion of the vehicle (n = 4 experiments), but this is statistically significant only for the first 5 min of the postinfusion period. In contrast, flow resistance in the heparinase infusion experiments (n = 6) exhibited a significant and sustained decrease during the observation period that ranged from 30 to 60 min in individual experiments.
|
|
Microinfusion of neuraminidase into one daughter branch of arteriolar bifurcations led to a significant elevation of flow resistance of the treated microvessel network already in the first measurement after the end of the microinfusion and a further progressive increase with time (Fig. 4). Intravital microscopic inspection showed that this resistance increase was accompanied by adherence and rolling of large numbers of platelets on the endothelial surface in all vessel branches downstream of the infusion site.
|
Figure 5 compares absolute values of flow resistance obtained in the network experiments for the untreated state with those seen after microinfusion of heparinase. Although in all but one experiment a significant reduction of resistance was seen after 5 min of infusion, only a small additional effect was seen after 10 min.
|
To summarize the results of both experimental designs, changes in flow
resistance on treatment were averaged for each individual experiment
over the postinfusion observation period. Mean values (± SD) of
these averages are compared in Fig. 6 for
the different treatment groups. The infusion of vehicle as well as of
buffer solutions with altered osmolarity (bifurcation experiments) led to small but not significant increases of flow resistance. No change in
resistance was observed after injection of heparitin-sulfate lyase
(bifurcation experiments). In contrast, heparinase treatment resulted
in a substantial reduction of flow resistance in both the network
experiments (mean reduction 
20.8 ± 8.5%, 10-min
infusion; 16 ± 13.4%, 5-min infusion) and the bifurcation
experiments (14.2 ± 6.5%, 7-min infusion). These changes
were statistically significant. The average resistance increase for the
first 15 min after the end of the neuraminidase infusion was 98.5 ± 25% for the higher enzyme concentration tested (bifurcation
experiments).
|
The effect of alterations in blood flow rate by partial microocclusion
of the feed vessel on network flow resistance is shown in Fig.
7. Measured flow velocities in the feeding
arteriole were converted into pseudo-shear rates
(
) by
dividing by vessel diameter. If it is assumed that measured velocities
represent means over vessel cross sections and that velocity profiles
are parabolic, pseudo-shear rates may be converted to wall shear rates by multiplying by 8. Because these assumptions may not be valid, the
use of
values is preferable. At pseudo-shear rates in the feeding vessel below
~100 diameters/s, flow resistance increased to about twice the value
measured at high shear rates. This increase was seen both in the raw
data (not shown) and in data corrected for the hematocrit reduction
occurring during the occlusion procedure (Fig. 7). Data obtained over a
large range of systemic hematocrit (0.07-0.52) exhibit very
similar trends. This suggests that
HS does not substantially
influence the increase in network flow resistance at low levels of
.
|
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
The key finding of the present study is that heparinase microinfusion led to a sustained 14-21% decrease in flow resistance of microvascular networks downstream of the site of infusion. Such an effect was not found when enzyme-free vehicle or solutions of altered osmolarity were infused. If endothelial swelling or shrinking occurs during hypo- or hyperosmolar microperfusion, this effect is apparently rapidly reversed on reperfusion with normal blood and thus not detectable in the present experimental design. Heparitin-sulfate lyase led to no measurable decrease of flow resistance. After neuraminidase, a doubling in flow resistance was observed, consistent with the results of Mühleisen et al. (14) for the isolated perfused ileum. In the present experiments, microscopic observation showed the presence of a layer adjacent to the endothelium composed mainly of adherent and rolling thrombocytes.
Glycocalyx thickness. Changes in resistance imply changes either in the effective vessel diameter or the apparent blood viscosity. Because the amount of solution microinfused was very small (between 1 and 7 µl), the systemic concentration of the enzymes applied is probably negligible, and it can be assumed that the rheological properties of blood entering the experimental site on terminating the microinfusion were unaffected by the preceding treatment. In addition, the results obtained in the bifurcation experiments are independent of changes of systemic hemodynamic conditions including blood viscosity. Therefore, the observed changes in flow resistance most likely reflect changes in effective vessel diameter. The vessels investigated were fully dilated, and no pressure changes were seen after the end of microinfusion. Therefore, changes in morphological vessel diameter are unlikely. However, the decrease in network flow resistance after heparinase treatment could result from reduction of the thickness of the glycocalyx, leading to an increase of the effective vessel diameter available for red blood cell and plasma motion.
The increase in effective vessel diameter that would be required to produce the observed decrease in resistance may be estimated using a theoretical simulation of flow in microvascular networks (22). This simulation uses geometries (diameters and lengths of the vessels, network topologies) determined previously (22) for networks in the rat mesentery of a size similar to the networks studied in the present study and assumes a relationship between apparent blood viscosity, vessel diameter, and hematocrit deduced from studies of blood flow in mesenteric networks (23). According to this simulation, a uniform increase of effective radius in all perfused microvessels of ~0.35 µm could account for the observed reduction of flow resistance in the bifurcation experiments on microinfusion of heparinase. For the network experiments, a value of ~0.55 µm is obtained. These values represent lower bounds on the thickness of the layer present on the endothelial surface in the untreated state. Equivalent reductions in resistance could also result from a nonuniformly distributed increase in diameter. In that case, the increase in effective radius would be larger than the above estimates in some parts of the networks and smaller in others. Because, for the purpose of this estimation, the glycocalyx is considered as a stiff, impermeable layer of uniform thickness lining all vessels in the network, the assumption of a permeable glycocalyx, permitting axial plasma flow (5), would increase these estimates. Also, the removal of the glycocalyx by the heparinase treatment was probably incomplete, because heparinase acts at specific sites within the oligosaccharide side chains of glycoproteins residing on the endothelial surface and does not cleave other (nonsulfated) sugar components or the protein backbone of these molecules. The above estimates of glycocalyx thickness are consistent with results of previous studies. On the basis of measurements of capillary hematocrit in resting striated muscle, Duling and Desjardins (7) suggested that plasma flow is retarded in a layer on the endothelial surface, the thickness of which was estimated between 0.8 and 1.8 µm. Further studies (6) showed that treatment with heparinase caused a persistent increase in capillary hematocrit, indicating a reduction in the thickness of the layer. Using a different approach, Vink and Duling (33) observed capillaries in the hamster cremaster muscle and demonstrated a layer of 0.4-0.5 µm adjacent to the endothelial cells that was inaccessible to flowing red blood cells and plasma. In contrast, the apparent glycocalyx thickness seen in electron microscopic studies is <0.1 µm (8, 15). However, electron microscopy requires fixation and staining procedures that may cause collapse of the glycocalyx proteoglycans (6). Indirect methods have led to higher estimates of layer thickness. From measurements of the sialic acid concentration on the surface of vascular endothelium (2), Silberberg (29) estimated a thickness of the glycocalyx gel under native conditions of at least 0.5 µm and noted that this gel would collapse to ~0.05 µm if dehydrated during preparation for electron microscopy.Possible contribution of plasma proteins to glycocalyx properties.
Endothelial cells bind plasma proteins, including fibrinogen and
albumin (26, 37). Observations of endothelium-coated beads sedimenting
in different media (24) imply that plasma proteins affect fluid flow
past endothelial cells. Surprising reductions of falling velocities
from expected values were found in plasma but not in other media. Based
on Stokes' law for the drag on a sphere, the reduction in
sedimentation velocity in plasma can be interpreted as an increase in
the effective radius of the beads by ~25 µm. Formation of a layer
of this thickness capable of impeding flow may depend on the low fluid
shear rate on the surface of the falling beads (<3.5
s1) compared with average
wall shear rates in the microvessels in the mesentery
(~200-2,000 s1; Ref.
21).
/L, where is the shear
elastic modulus of the membrane and L
is a characteristic length scale. Taking = 0.006 dyn/cm and
L = 1 µm yields 60 dyn/cm2; a similar estimate is
implied by more detailed calculations (27). An increase in colloid
osmotic pressure within the glycocalyx by only 1% (i.e., 330 dyn/cm2, based on a colloid
osmotic pressure of 25 mmHg) could thus generate sufficient force to
resist penetration by red blood cells. The finding that short-term
microinfusion of artificial plasmas with altered protein content had
little effect on capillary hematocrit (10) may indicate that
equilibration of proteins between plasma and glycocalyx exhibits time
constants above ~10 min.
Effect of flow rate on flow resistance.
When blood flow rate was reduced by graded microocclusion, network flow
resistance remained approximately constant at
levels
down to ~100 s1 in the
feeding arterioles (Fig. 7). However, flow resistance increased at flow
rates below this level. The resistance increase at low shear rates was
similar for all levels of systemic hematocrit (range 0.07-0.52)
and seems therefore to be independent of red blood cell concentration.
in the
range from 1 to 100 s1 (1,
25). Because average
values in
venules with diameters >20 µm are about one-eighth of those in the
feeding arteriole (21), the threshold
level of
100 s1 in the feeding
arteriole corresponds to ~12
s1 in larger venules.
Therefore, the observed increase in resistance is not accounted for by
the rheological behavior of blood in narrow uniform tubes.
2) The observed increase of
resistance on microocclusion could result from a passive diameter
change caused by the reduction of capillary pressure. Bosman et al. (3)
showed passive changes in capillary diameter by 6% and +12%
during aortic occlusion causing a fall of capillary pressure and
reactive hyperemia causing an elevation of capillary pressure. Such
diameter changes are too small to explain the resistance increase of up
to 100% observed in the present experiments with decreasing shear
rate. 3) The thickness of the
glycocalyx may increase at very low flow rates ( < 100 s1). Desjardins and
Duling (6) reported that capillary hematocrit in muscle capillaries
increased with flow velocity from ~0.18 to 0.27 mm/s. Capillary
velocities in this range correspond to those at which flow-dependent
resistance was evident in the present study. This last mechanism is
therefore consistent with observed flow dependence of flow resistance
observed here.
Discrepancy between in vivo and in vitro estimates of network flow resistance. Measured values of flow resistance in microvascular networks have been found to be about twice as large as expected from measurements of flow resistance in glass tubes (23). Flow restriction by the glycocalyx is a possible reason for this difference. The relation between glycocalyx thickness and network flow resistance can be estimated using the theoretical simulation already described. According to this simulation, a uniform, impermeable glycocalyx of 1.5-µm thickness would produce the difference in the flow resistance of microvascular networks of the rat mesentery compared with predictions based on glass tube rheology.
In reality, however, other effects may also contribute to the increased flow resistance in vivo. The hydrodynamic resistance of a vessel with irregular luminal contour is larger than the resistance of a uniform tube with the same mean diameter (20) because contour irregularity leads to additional energy dissipation caused by transient deformation of red blood cells (28). Additional flow resistance may occur at vascular branch points (28). Available estimates of these effects suggest that they may cause a reduction of effective vessel radius by not more than ~0.5 µm. The effect of white blood cells on flow resistance of vascular beds has been debated, and reported resistance increases caused by white blood cells in skeletal muscle range from 1 to 20% (4, 34, 35). In the mesentery, capillaries are wider than in skeletal muscle and effects of white blood cells on resistance can be expected to be lower. Thus the observed difference between flow resistance in vivo and in vitro is only partly explained by effects of vascular irregularity, entrance phenomena, and white blood cells. The remaining discrepancy can, however, be accounted for by the presence of a stiff, impermeable layer with thickness of >0.5 µm adjacent to the endothelium. In conclusion, the present findings support the concept of a macromolecular layer (glycocalyx) at the luminal surface of microvascular endothelium that contributes significantly to microvascular flow resistance. This layer may have significant implications for the many physiological functions in which endothelial cells are involved. Such functions could therefore be affected by changes in plasma protein composition that modify the composition and thus relevant properties of the endothelial glycocalyx.| |
ACKNOWLEDGEMENTS |
|---|
The expert technical help of B. Giesicke and M. Ehrlich as well as the assistance of A. Scheuermann in preparing the manuscript are gratefully acknowledged.
| |
FOOTNOTES |
|---|
This study was supported by the Deutsche Forschungsgemeinschaft (Pr 271/1-1, 1-2, 5-1, and 5-2) and by National Heart, Lung, and Blood Institute Grant HL-34555.
Address for reprint requests: A. R. Pries, Freie Universität Berlin, Dept. of Physiology, Arnimallee 22, D-14195 Berlin, Germany.
Received 20 February 1997; accepted in final form 30 July 1997.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
1.
Alonso, C.,
A. R. Pries,
O. Kiesslich,
D. Lerche,
and
P. Gaehtgens.
Transient rheological behavior of blood in low-shear tube flow: velocity profiles and effective viscosity.
Am. J. Physiol.
268 (Heart Circ. Physiol. 37):
H25-H32,
1995
2.
Born, G. V. R.,
and
W. Palinski.
Unusually high concentrations of sialic acids on the surface of aortic endothelium.
Br. J. Exp. Pathol.
66:
543-549,
1985[Medline].
3.
Bosman, J.,
G.-J. Tangelder,
M. G. A. Oude Egbrink,
R. S. Reneman,
and
D. W. Slaaf.
Capillary diameter changes during low perfusion pressure and reactive hyperemia in rabbit skeletal muscle.
Am. J. Physiol.
269 (Heart Circ. Physiol. 38):
H1048-H1055,
1995
4.
Braide, M.,
B. Amundson,
S. Chien,
and
U. Bagge.
Quantitative studies on the influence of leukocytes on the vascular resistance in a skeletal muscle preparation.
Microvasc. Res.
27:
331-352,
1984[Medline].
5.
Damiano, E. R.,
B. R. Duling,
K. Ley,
and
T. C. Skalak.
Axisymmetric pressure-driven flow of rigid pellets through a cylindrical tube lined with a deformable porous layer.
J. Fluid Mech.
314:
163-189,
1996.
6.
Desjardins, C.,
and
B. R. Duling.
Heparinase treatment suggests a role for the endothelial cell glycocalyx in regulation of capillary hematocrit.
Am. J. Physiol.
258 (Heart Circ. Physiol. 27):
H647-H654,
1990
7.
Duling, B. R.,
and
C. Desjardins.
Capillary hematocrit
what does it mean?
News Physiol. Sci.
2:
66-69,
1987.
8.
Haldenby, K. A.,
D. C. Chappell,
C. P. Winlove,
K. H. Parker,
and
J. A. Firth.
Focal and regional variations in the composition of the glycocalyx of large vessel endothelium.
J. Vasc. Res.
31:
2-9,
1994[Medline].
9.
Intaglietta, M.,
and
W. R. Tompkins.
Micropressure measurements with 1 micron and smaller cannulae.
Microvasc. Res.
3:
211-214,
1971[Medline].
10.
Keller, M. W.,
D. N. Damon,
and
B. R. Duling.
Determination of capillary tube hematocrit during arteriolar microperfusion.
Am. J. Physiol.
266 (Heart Circ. Physiol. 35):
H2229-H2238,
1994
11.
Ley, K.,
P. Gaehtgens,
C. Fennie,
M. S. Singer,
L. A. Lasky,
and
S. D. Risen.
Lectin-like cell adhesion molecule 1 mediates leukocyte rolling in mesenteric venules in vivo.
Blood
77:
2553-2555,
1991
12.
Lipowsky, H. H.,
S. Kovalcheck,
and
B. W. Zweifach.
The distribution of blood rheological parameters in the microcirculation of cat mesentery.
Circ. Res.
43:
738-749,
1978
13.
Lipowsky, H. H.,
S. Usami,
and
S. Chien.
In vivo measurements of "apparent viscosity" and microvessel hematocrit in the mesentery of the cat.
Microvasc. Res.
19:
297-319,
1980[Medline].
14.
Mühleisen, H.,
G. V. R. Born,
and
C. C. Michel.
Effects of neuraminidase on vascular resistance under conditions of maximum vasodilatation in the isolated perfused rat ileum (Abstract).
J. Physiol. (Lond.)
430:
38P,
1990.
15.
Pino, R. M.
The cell surface of a restrictive fenestrated endothelium. II. Dynamics of cationic ferritin binding and the identification of heparin and heparan sulfate domains on the choriocapillaris.
Cell Tissue Res.
243:
157-164,
1986[Medline].
16.
Pries, A. R.
A versatile video image analysis system for microcirculatory research.
Int. J. Microcirc. Clin. Exp.
7:
327-345,
1988[Medline].
17.
Pries, A. R.,
G. Kanzow,
and
P. Gaehtgens.
Microphotometric determination of hematocrit in small vessels.
Am. J. Physiol.
245 (Heart Circ. Physiol. 14):
H167-H177,
1983.
18.
Pries, A. R.,
K. Ley,
M. Claassen,
and
P. Gaehtgens.
Red cell distribution at microvascular bifurcations.
Microvasc. Res.
38:
81-101,
1989[Medline].
19.
Pries, A. R.,
D. Neuhaus,
and
P. Gaehtgens.
Blood viscosity in tube flow: dependence on diameter and hematocrit.
Am. J. Physiol.
263 (Heart Circ. Physiol. 32):
H1770-H1778,
1992
20.
Pries, A. R.,
D. Schönfeld,
P. Gaehtgens,
M. F. Kiani,
and
G. R. Cokelet.
Diameter variability and microvascular flow resistance.
Am. J. Physiol.
272 (Heart Circ. Physiol. 41):
H2716-H2725,
1997
21.
Pries, A. R.,
T. W. Secomb,
and
P. Gaehtgens.
Structure and hemodynamics of microvascular networks: heterogeneity and correlations.
Am. J. Physiol.
269 (Heart Circ. Physiol. 38):
H1713-H1722,
1995
22.
Pries, A. R.,
T. W. Secomb,
P. Gaehtgens,
and
J. F. Gross.
Blood flow in microvascular networks: experiments and simulation.
Circ. Res.
67:
826-834,
1990
23.
Pries, A. R.,
T. W. Secomb,
T. Gessner,
M. Sperandio,
J. F. Gross,
and
P. Gaehtgens.
Resistance to blood flow in microvessels in vivo.
Circ. Res.
75:
904-915,
1994
24.
Reinhart, W. H.,
C. M. Boulanger,
T. F. Lüscher,
A. Haeberli,
and
P. W. Straub.
Influence of endothelial surface on flow velocity in vitro.
Am. J. Physiol.
265 (Heart Circ. Physiol. 34):
H523-H529,
1993
25.
Reinke, W.,
P. Gaehtgens,
and
P. C. Johnson.
Blood viscosity in small tubes: effect of shear rate, aggregation, and sedimentation.
Am. J. Physiol.
253 (Heart Circ. Physiol. 22):
H540-H547,
1987
26.
Schneeberger, E. E.,
and
M. Hamelin.
Interaction of serum proteins with lung endothelial glycocalyx: its effect on endothelial permeability.
Am. J. Physiol.
247 (Heart Circ. Physiol. 16):
H206-H217,
1984
27.
Secomb, T. W.
Flow-dependent rheological properties of blood in capillaries.
Microvasc. Res.
34:
46-58,
1987[Medline].
28.
Secomb, T. W.,
and
R. Hsu.
Motion of red blood cells in capillaries with variable cross-sections.
J. Biomech. Eng.
118:
538-544,
1996[Medline].
29.
Silberberg, A. The physiological role of a thick gel-like
layer over the endothelial surface (Abstract).
Int. J. Microcirc. Clin.
Exp. 9, Suppl. 1: 204, 1990.
30.
Silberberg, A.
Polyelectrolytes at the endothelial cell surface.
Biophys. Chem.
41:
9,
1991[Medline].
31.
Suárez, J.,
and
R. Rubio.
Regulation of glycolytic flux by coronary flow in guinea pig heart. Role of vascular endothelial cell glycocalyx.
Am. J. Physiol.
261 (Heart Circ. Physiol. 30):
H1994-H2000,
1991
32.
Turner, M. R.,
G. Clough,
and
C. C. Michel.
The effects of cationised ferritin and native ferritin upon the filtration coefficient of single frog capillaries. Evidence that proteins in the endothelial cell coat influence permeability.
Microvasc. Res.
25:
205-222,
1983[Medline].
33.
Vink, H.,
and
B. R. Duling.
Identification of distinct luminal domains for macromolecules, erythrocytes and leukocytes within mammalian capillaries.
Circ. Res.
79:
581-589,
1996
34.
Warnke, K. C.,
and
T. C. Skalak.
The effects of leukocytes on blood flow in a model skeletal muscle capillary network.
Microvasc. Res.
40:
118-136,
1990[Medline].
35.
Warnke, K. C.,
and
T. C. Skalak.
Leukocyte plugging in vivo in skeletal muscle arteriolar trees.
Am. J. Physiol.
262 (Heart Circ. Physiol. 31):
H1149-H1155,
1992
36.
Wiederhielm, C. A.,
and
L. L. Black.
Osmotic interaction of plasma proteins with interstitial macromolecules.
Am. J. Physiol.
231:
638-641,
1976.
37.
Witte, S.
The influence of the fibrinolytic system on the affinity of fibrinogen for the endothelial-plasma interface.
Thromb. Res.
52:
111-117,
1988[Medline].
This article has been cited by other articles:
|
|
 |
|
  J. W. G. E. VanTeeffelen, A. A. Constantinescu, J. Brands, J. A. E. Spaan, and H. Vink Bradykinin- and sodium nitroprusside-induced increases in capillary tube haematocrit in mouse cremaster muscle are associated with impaired glycocalyx barrier properties J. Physiol., July 1, 2008; 586(13): 3207 - 3218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Van Teeffelen, H. Vink, B. T. Ameredes, A. M. Jones, S. Egginton, L. F. Ferreira, G. W. Schmid-Schoenbein, W. L. Murfee, S. S. Segal, K. Tyml, et al. J Appl Physiol, March 1, 2008; 104(3): 895 - 899. [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Stevens, V. Hlady, and R. O. Dull Fluorescence correlation spectroscopy can probe albumin dynamics inside lung endothelial glycocalyx Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L328 - L335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Westerhof, C. Boer, R. R. Lamberts, and P. Sipkema Cross-talk between cardiac muscle and coronary vasculature. Physiol Rev, October 1, 2006; 86(4): 1263 - 1308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. G. E. VanTeeffelen, S. Dekker, D. S. Fokkema, M. Siebes, H. Vink, and J. A. E. Spaan Hyaluronidase treatment of coronary glycocalyx increases reactive hyperemia but not adenosine hyperemia in dog hearts Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2508 - H2513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Pries and T. W. Secomb Microvascular blood viscosity in vivo and the endothelial surface layer Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2657 - H2664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Zuurbier, C. Demirci, A. Koeman, H. Vink, and C. Ince Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells J Appl Physiol, October 1, 2005; 99(4): 1471 - 1476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsumoto, T. Asano, K. Mano, H. Tachibana, M. Todoh, M. Tanaka, and F. Kajiya Regional myocardial perfusion under exchange transfusion with liposomal hemoglobin: in vivo and in vitro studies using rat hearts Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1909 - H1914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Ainslie, J. S. Garanich, R. O. Dull, and J. M. Tarbell Vascular smooth muscle cell glycocalyx influences shear stress-mediated contractile response J Appl Physiol, January 1, 2005; 98(1): 242 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ueda, M. Shimomura, M. Ikeda, R. Yamaguchi, and K. Tanishita Effect of glycocalyx on shear-dependent albumin uptake in endothelial cells Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2287 - H2294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Mulivor and H. H. Lipowsky Inflammation- and ischemia-induced shedding of venular glycocalyx Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1672 - H1680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Platts and B. R. Duling Adenosine A3 Receptor Activation Modulates the Capillary Endothelial Glycocalyx Circ. Res., January 9, 2004; 94(1): 77 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Florian, J. R. Kosky, K. Ainslie, Z. Pang, R. O. Dull, and J. M. Tarbell Heparan Sulfate Proteoglycan Is a Mechanosensor on Endothelial Cells Circ. Res., November 14, 2003; 93 (10): e136 - e142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Jeansson and B. Haraldsson Glomerular Size and Charge Selectivity in the Mouse after Exposure to Glucosaminoglycan-Degrading Enzymes J. Am. Soc. Nephrol., July 1, 2003; 14(7): 1756 - 1765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Platts, J. Linden, and B. R. Duling Rapid modification of the glycocalyx caused by ischemia-reperfusion is inhibited by adenosine A2A receptor activation Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2360 - H2367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Osterloh, U. Ewert, and A. R. Pries Interaction of albumin with the endothelial cell surface Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H398 - H405. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
