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A R Pries

Publications and source records attributed to A R Pries.

At least 19 recordsLinked to original sources

Flow-dependent regulation of arteriolar diameter in rat skeletal muscle in situ: role of endothelium-derived relaxing factor and prostanoids.

1. Arteriolar diameter in the resting rat spinotrapezius muscle was studied by intravital video microscopy before and after blockade of the L-arginine-EDRF (NG-nitro-L-arginine, L-NNA) or the cyclo-oxygenase-prostacyclin (indomethacin) pathway. Blockade of either pathway leads to a decrease of arteriolar diameter of 25-40%, while the combined blockade of both results in vasoconstriction of 50-60%. 2. Alteration of blood flow velocity elicited by partial micropipette occlusion induces corresponding changes of vessel diameter. The flow-dependent diameter response is reduced by about 80% by L-NNA. By contrast, blockade of prostanoid production shows no significant influence on vessel response to blood flow alteration in the range tested. 3. Transient overshooting vasodilatation is seen for about 1 min following the sudden restoration of flow velocity subsequent to occlusion. In contrast to the initial phase of this response, the late phase is blocked by L-NNA. 4. The findings suggest that basal release of endothelium-derived relaxing factor (EDRF) and prostanoids leads to additive and independent dilator effects, and that flow-dependent diameter changes are primarily mediated by EDRF. 5. If present data are compared with literature reports, it appears that arterial flow sensitivity is most pronounced in the smallest vessels. In such vessels, flow-dependent dilatation will amplify even small changes of volume flow by more than four times.

Animals

Effect of oxygen tension on regulation of arteriolar diameter in skeletal muscle in situ.

Skeletal muscle arterioles are known to constrict upon elevation of ambient PO2. While several studies have shown that the endothelium plays an important role in this response, it is not clear how this response is mediated. We examined the oxygen-induced constriction of arterioles in the rat spinotrapezius muscle. Elevation of superfusion solution PO2 from about 15 to 150 mm Hg caused arteriolar constriction by 25% (+/- 3%, n = 18). Inhibition of prostaglandin synthesis by superfusion of indomethacin (30 microM) produced vasoconstriction by 28% (+/- 9.5%, n = 5), but left the PO2 response unaffected. Blockade of the synthesis of endothelium-derived relaxing factor (EDRF) by NG-nitro-L-arginine (L-NNA, 35 mg/kg i.v.) caused arteriolar constriction by 31% (+/- 8%, n = 8). During application of L-NNA, the constrictor response to PO2 elevation was reduced to 3 +/- 2%. Administration of superoxide dismutase (SOD, 80,000 U/kg i.v.) did not affect the PO2 response. It is concluded that in small arterioles of skeletal muscle both EDRF and prostanoids sustain a significant basal dilatation. The dilatory effects of EDRF but not of prostaglandins are strongly dependent on PO2. The vasoconstriction in response to high ambient PO2 is not due to EDRF breakdown during its diffusion from endothelial to smooth muscle cells.

Animals

Transient rheological behavior of blood in low-shear tube flow: velocity profiles and effective viscosity.

Velocity profiles of human blood flowing through vertical and horizontal glass tubes (25-100 microns ID) were measured as a function of time following a sudden reduction of wall shear stress (tau w) from a high value to values ranging from 2 to 100 mPa. Cell velocities at various radial positions were determined off-line from video recordings by digital image analysis. In vertical tubes, symmetric velocity profiles were obtained that developed increasing bluntness with time, particularly at lower tau w and in smaller tubes. In horizontal tubes, velocity profiles developed strong asymmetry as a function of time. Red blood cell (RBC) sedimentation was associated with uniform low flow velocities in the concentrating cell sediment, whereas faster flow and almost parabolic profiles were observed in the supernatant plasma region. Calculations of effective blood viscosity showed a decrease with time at low tau w in vertical tubes but an increase in horizontal tubes. The differences between profile shape and effective viscosity in vertical and horizontal tubes disappeared at tau w > 50 mPa. These findings are related to the cross-sectional distribution of RBC, which depends on RBC aggregation and sedimentation.

Blood Flow Velocity

Structure and hemodynamics of microvascular networks: heterogeneity and correlations.

The objective of this study was to quantify the heterogeneity of topological, morphological, and hemodynamic parameters in microvascular networks and to identify functionally relevant correlations among these parameters. Seven networks in the rat mesentery (383-913 vessel segments per network) were examined, and measurements were made of segment generation, diameter, length, and hematocrit in all segments (n = 3,129) and of flow velocity (only in 3 networks, 1,321 segments). In addition, hematocrit, flow rate, and pressure were derived for all segments from a mathematical simulation. All parameters obtained exhibit heterogeneous distributions with coefficients of variation ranging from 0.28 (capillary diameter) to > 1.5 (volume flow and pressure gradient). Several strong correlations exist between parameters, e.g., discharge hematocrit increases with vessel diameter, and shear rate increases with intravascular pressure. Because of such correlations, the extrapolation from average values for "typical vessels" to network properties can lead to substantial errors. For example, the mean network transit time estimated based on averaged quantities is 6.5 s, which is about 60% higher than the true value (4.08 s). Simplified models of the vascular bed may therefore be inadequate to describe functional properties of the microcirculation.

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Design principles of vascular beds.

Hemodynamic parameters were determined in each vessel segment of six complete microvascular networks in the rat mesentery by using a combination of experimental measurements and theoretical stimulations. For a total number of 2592 segments, a strong unified dependence of wall shear stress on intravascular pressure for arterioles, capillaries, and venules was obtained. All three types of segments exhibit an essentially identical variation of shear stress from high to low values (from approximately 100 to 10 dyne/cm2) as intravascular pressure falls from 70 to 15 mm Hg. On the basis of these observations, it is proposed that vascular beds grow and adapt so as to maintain the shear stress in each vessel at a level that depends on local transmural pressure. In contrast to Murray's classic 'minimum-cost' hypothesis, which implies uniformity of wall shear rate throughout the vasculature, the proposed design principle provides an explanation for the functionally important arteriovenous asymmetry of wall shear rates and flow resistance in the circulation.

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Fluctuations in microvascular blood flow parameters caused by hemodynamic mechanisms.

We have developed a mathematical model of microvascular network blood flow in which the nonlinear flow properties of blood and the nonuniform axial distribution of red blood cells in each vessel, as well as disproportionate cell partitioning at bifurcations, are all accounted for. The movements of red blood cells in the network are tracked; hence, the model is able to simulate temporal variations in local flow parameters in the network due to hemodynamic mechanisms. The model was applied to four rat mesenteric networks for which the topology, boundary conditions, blood velocity, and discharge hematocrit (Hctd) had been measured for each branch. Temporal variations in Hctd and blood velocity after simulation convergence were predicted. In some cases of the three vessels connected to a node, Hctd of one vessel fluctuates in a simple periodic form, Hctd of the second one oscillates in a more complex periodic form, whereas the Hctd of the third one does not oscillate at all. These variations were obtained with constant flow boundary conditions and, therefore, are due to hemodynamic factors alone. The temporal variations in flow parameters predicted by the model simulations are caused by hemorheological mechanisms and would be superimposed on variations caused by other mechanisms (e.g., vasomotion). The frequencies of the predicted fluctuations in blood velocity are in qualitative agreement with observed in vivo variations in dual-slit velocity in the arterioles of the cremaster muscle of anesthetized Golden hamster.

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Resistance to blood flow in microvessels in vivo.

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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Time-dependent rheological behavior of blood at low shear in narrow vertical tubes.

The time-dependent flow behavior of normal human blood after a sudden reduction of wall shear stress from 5,000 mPa to a low level (2-100 mPa) was studied during perfusion of vertical tubes (internal diam 28-101 microns) at constant driving pressures. Immediately after the implementation of low-shear flow conditions the concentration of red blood cells (RBCs) near the tube wall started to decrease, and marginal plasma spaces developed as a result of the assembly of RBC aggregates. This was associated with a time-dependent increase of flow velocity by up to 200% within 300 s, reflecting a reduction of apparent viscosity. These time-dependent changes of flow behavior increased strongly with decreasing wall shear stress and with increasing tube diameter. A correlation between the width of the marginal plasma layer and relative apparent viscosity was obtained for every condition of tube diameter, wall shear stress, and time. Time-dependent changes of blood rheological properties could be relevant in the circulation, where the blood is exposed to rapid and repeated transitions from high-shear flow conditions in the arterial and capillary system to low-shear conditions in the venous system.

Blood Flow Velocity

Distribution of microvascular pressure in arteriolar vessel trees of ventilated rabbit lungs.

We have developed a new in vivo microscopic technique for comprehensive measurements of vessel diameter, segment length, and red blood cell velocity in discrete arteriolar vessel trees of the lung. In anesthetized and mechanically ventilated rabbits, a transparent window was implanted into the right thoracic wall. We injected fluorescently labeled red cells to visualize blood flow and to measure red blood cell velocity. The distribution of microvascular pressures was simulated in a computer model based on morphometric and microhemodynamic data. Of the total pulmonary vascular pressure drop from pulmonary artery to left atrium, on average 2.5% occurred in distal arteriolar vessel trees with main trunk diameters of 73-111 microns. Along the pathlength from main trunk to terminal arterioles (0.18-2.79 mm), the pressure drop ranged between 0.06 and 0.94 mmHg. The pressure drop along individual pathways correlated significantly with pathlength of terminal arterioles, whereas red blood cell velocity did not. The results indicate that in terminal arteriolar vessel trees of the ventilated rabbit lung the resistance to blood flow is low, and the heterogeneity of microvascular pressures in arterioles feeding capillary networks is high.

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Blood viscosity in tube flow: dependence on diameter and hematocrit.

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 apparent viscosity of blood in tube flow depends on tube diameter. Quantitative descriptions of this effect and of the dependence of blood viscosity on hematocrit in the different diameter tubes are required for the development of hydrodynamic models of blood flow through the microcirculation. The present study provides a comprehensive data base for the description of relative apparent blood viscosity as a function of tube diameter and hematocrit. Data available from the literature are compiled, and new experimental data obtained in a capillary viscometer are presented. The combined data base comprises measurements at high shear rates (u > or = 50 s-1) in tubes with diameters ranging from 3.3 to 1,978 microns at hematocrits of up to 0.9. If corrected for differences in suspending medium viscosity and temperature, the data show remarkable agreement. Empirical fitting equations predicting relative apparent blood viscosity from tube diameter and hematocrit are presented. A pronounced change in the hematocrit dependence of relative viscosity is observed in a range of tube diameters in which viscosity is minimal. While a linear hematocrit-viscosity relationship is found in tubes of < or = 6 microns, an overproportional increase of viscosity with hematocrit prevails in tubes of > or = 9 microns. This is interpreted to reflect the hematocrit-dependent transition from single- to multifile arrangement of cells in flow.

Animals

Redistribution of red blood cell flow in microcirculatory networks by hemodilution.

The effect of isovolemic hemodilution on red blood cell flow distribution was studied in complete self-contained microvessel networks of the rat mesentery. Hematocrit, diameter, and length of all vessel segments as well as the topological structure were determined in control networks (systemic hematocrit, 0.54) and after hemodilution (systemic hematocrit, 0.30). Hemodilution was performed by exchanging blood with hydroxyethyl starch (MW 450,000; 6%) or homologous plasma. With hemodilution, the decrease of microvessel hematocrit exceeded that of systemic hematocrit. The average discharge hematocrit in capillaries was 79% of systemic hematocrit in the control group and 73% with hemodilution (p less than 0.001). The heterogeneity of capillary hematocrit within the network, expressed by the coefficient of variation, increased from 0.4 to 0.7. By using the morphological and topological data of four networks, the distribution of hematocrits was also calculated using a hydrodynamic flow model. The modeling results were found to be in close agreement with the experimental data. This indicates that the observed changes can be deduced from established rheological phenomena, most of all phase separation at arteriolar bifurcations. The changes in hematocrit distribution after hemodilution are accompanied by a redistribution of red blood cell flow within the network: relative to total red blood cell flow, red blood cell flow in the distal capillaries of the network increases by about 40% at the expense of the proximal capillaries that are close to the feeding arteriole and that exhibit the highest red blood cell flow under control conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

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A new approach to intravital videomicroscopy of rat spinotrapezius muscle.

A modified preparation of the rat spinotrapezius muscle is described in which optimal conditions for intravital microscopy can be achieved while the supplying blood vessels are left fully intact, and mechanical stress to the muscle during preparation is reduced to an unavoidable minimum. The viability of the preparation is demonstrated using the response of arterial microvessels to endothelium-dependent and -independent dilators and to changes of ambient PO2, the presence of spontaneous vasomotion, and histochemical analysis of pertinent enzyme systems. The preparation is viable for much longer experimental time periods (up to 10 hours) than reported previously, provided the intensity of illumination is kept at a very low level. If the latter prerequisite is met, tissue edema, maximal vasodilation, and the associated loss of responsiveness to vasoactive stimuli of arterioles is reliably avoided.

Animals

Blood flow in microvascular networks. Experiments and simulation.

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.

Animals

Venulo-arteriolar communication and propagated response. A possible mechanism for local control of blood flow.

The effect of microinjection of norepinephrine (10(-5) M) into precapillary microvessels of the rat mesentery was studied using intravital microscopy. Upon application, in 29 out of 40 cases (73%) flow ceased at the site of drug application, although in most cases the precapillary microvessels themselves did not show a diameter change due to a lack of smooth muscle cells as confirmed by transmission electron microscopy. In 17 out of the 29 cases with flow cessation (59%), an intimate contact between the venule draining the site of application and the supplying arteriole was found. Initial constriction was seen at the site where the venule crossed the arteriole. Constriction propagated both up- and downstream along the arteriole, and also across arteriolo-arteriolar arcades. Arteriolar constriction could be abolished by intentionally occluding the venule draining the norepinephrine solution. It is proposed that venuloarteriolar contacts and propagated vasomotor response may contribute to local blood flow regulation by providing a feedback loop between tissue capillaries and resistance arterioles. In three complete mesenteric microvessel networks, the arterioles (n = 34) supplying 273 out of 401 capillaries (68%) were in close proximity to venules draining these same capillaries. Each of these arterioles served, on average, 43 capillaries, showing a bimodal distribution with peaks at 4 to 16 and at 64 to 256 capillaries. On average, 62% of all capillaries drained by a given venule crossing an arteriole originated from this very arteriole, indicating a reasonably effective feedback.

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Red cell distribution at microvascular bifurcations.

The distribution of red cell and blood volume flow was studied at 65 arteriolar bifurcations in the rat mesentery. Hematocrit and flow velocity were measured simultaneously in all three vessel segments constituting a bifurcation. Blood flow distribution was manipulated by irreversibly occluding downstream side branches of one of the daughter vessels. The dependence of fractional red cell volume flow on fractional blood flow was described using a three-parameter (X0, B, A) logit function. The critical volume flow fraction below which only plasma enters a downstream branch (X0), the nonlinearity of the relation between red cell and blood volume flow (B), and the asymmetry of that relation which is described by the parameter A decrease with increasing diameter of the vessel feeding the bifurcation. At diameters above 30 microns, phase separation is very limited. In addition, the nonlinearity parameter B decreases with decreasing hematocrit in the feeding vessel. The asymmetry parameter A strongly depends on the diameter ratio between the two daughter branches: For a given fractional blood flow, the smaller branch receives more red cells than the larger branch. Using a model for plasma skimming based on the assumption of a planar separating surface, the shape of the radial hematocrit profile in the feeding vessel has been calculated. The model predicts a decrease in local hematocrit from the vessel axis toward the wall with a distinct marginal zone free from cell centers. With increasing vessel diameter the hematocrit profile becomes more blunted while the width of the marginal zone increases.

Animals

Time-dependent rheological behaviour of blood flow at low shear in narrow horizontal tubes.

Magnitude and time-dependence of the effects of red cell aggregation and sedimentation on the rheology of human blood were studied during low shear (tau W 2.5 to 92 mPa) flow through horizontal tubes (ID 25 to 105 microns). Immediately following reduction of perfusion pressure to a low value the red cell concentration near the tube walls decreases as a result of red cell aggregation. This is associated with a transient increase of centerline velocity. Simultaneously, sedimentation begins to occur and eventually leads to the formation of a cell-free supernatant plasma layer. Time-course and extent of this sedimentation process are strongly affected by wall shear stress variation, particularly in the larger tubes. At the lower shear stresses, centerline velocity decreases (flow resistance increases) with time following the initial acceleration period, due to sedimentation of red cells. This is followed by a further increase of resistance caused by the elevation of hematocrit occurring because of the reduction of cell/plasma velocity ratio. The time dependence of blood rheological behaviour under these flow conditions is interpreted to reflect the net effect of the partially counteracting phenomena of sedimentation and red cell aggregation.

Blood Flow Velocity

Preferential distribution of leukocytes in rat mesentery microvessel networks.

Distribution of leukocytes in rat mesenteric microvessel networks was studied using intravital fluorescence video microscopy. A digital image analysis system was used to measure vessel diameters, flow velocities and leukocyte fluxes in 306 capillaries of 8 networks. Capillaries were defined as vessel segments connecting divergent to convergent branch points. Their topological position within the network was quantified by a generation number defined as the number of bifurcations between the capillary and the arteriole feeding the network. Proximal capillaries (generation numbers 4 and 5) were slightly but significantly smaller in diameter (8.9 +/- 0.4 micron, mean +/- SEM) than distal ones (generation numbers 20 and 21, 10.1 +/- 0.4 micron). Average capillary flow velocity decreased markedly from 2.0 +/- 1.0 mm.s-1 in proximal to 0.41 +/- 0.06 mm.s-1 in distal capillaries. Average leukocyte concentration was 3.4 +/- 0.5.10(9) 1(-1) and thus significantly below systemic values (6.0.10(9) 1(-1] in proximal capillaries, and above in distal ones (11.7 +/- 2.6.10(9) 1(-1). The analysis of flow and leukocyte flux partition at 138 bifurcations showed preferential distribution of leukocytes to the daughter capillary with higher flow rate. This suggests a tentative explanation for the observed leukocyte accumulation along the microvascular tree: due to their low fractional flow, proximal capillaries draw relatively leukocyte-poor blood from the arteriole feeding the network; this leads to an increased leukocyte concentration in distal capillaries. As a consequence of the concomitant increase of capillary diameter with increasing generation number, leukocytes are preferentially flowing through larger capillaries and are excluded from small ones.

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