Experimental measurements of the temperature variation along artery-vein pairs from 200 to 1000 microns diameter in rat hind limb

Theoretical studies have indicated that a significant fraction of all blood-tissue heat transfer occurs in artery-vein pairs whose arterial diameter varies between 200 and 1000 microns. In this study, we have developed a new in vivo technique in which it is possible to make the first direct measurements of the countercurrent thermal equilibration that occurs along thermally significant vessels of this size. Fine wire thermocouples were attached by superglue to the femoral arteries and veins and their subsequent branches in rats and the axial temperature variation in each vessel was measured under different physiological conditions. Unlike the blood vessels < 200 microns in diameter, where the blood rapidly equilibrates with the surrounding tissue, we found that the thermal equilibration length of blood vessels between 200 microns and 1000 microns in diameter is longer than or at least equivalent to the vessel length. It is shown that the axial arterial temperature decays from 44% to 76% of the total core-skin temperature difference along blood vessels of this size, and this decay depends strongly on the local blood perfusion rate and the vascular geometry. Our experimental measurements also showed that the SAV venous blood recaptured up to 41% of the total heat released from its countercurrent artery under normal conditions. The contribution of countercurrent heat exchange is significantly reduced in these larger thermally significant vessels for hyperemic conditions as predicted by previous theoretical analyses. Results from this study, when combined with previous analyses of vessel pairs less than 200 microns diameter, enable one estimate the arterial supply temperature and the correction coefficient in the modified perfusion source term developed by the authors.     

Structure and functional properties of the arterial system of the frog submandibular muscle as an object for studying working hyperemia

Architectonics and ultrastructure of the arterial blood vessels of the frog submaxillary muscle are described. Intramuscular arterial vessels 100 divided by 8 micron in diameter have a single layer of smooth muscle cells (SMC), while SMC themselves look simplified and undifferentiated. The contacts between SMC in arterial vessels of all the sizes and myoendothelial contacts in the vessels 80-8 microns in diameter are noted. In the resting muscle, the arterial vessels of all the sizes show spontaneous changes in the diameter. During muscular contraction, the time course of the dilatation of different vessels is different, which is likely to be caused by vasomotion phase differences seen immediately before the contraction.     

Breaking symmetry in non-planar bifurcations: distribution of flow and wall shear stress

Non-planarity in blood vessels is known to influence arterial flows and wall shear stress. To gain insight, computational fluid dynamics (CFD) has been used to investigate effects of curvature and out-of-plane geometry on the distribution of fluid flows and wall shear stresses in a hypothetical non-planar bifurcation. Three-dimensional Navier-Stokes equations for a steady state Newtonian fluid were solved numerically using a finite element method. Non-planarity in one of the two daughter vessels is found to deflect flow from the inner wall of the vessel to the outer wall and to cause changes in the distribution of wall shear stresses. Results from this study agree to experimental observations and CFD simulations in the literature, and support the view that non-planarity in blood vessels is a factor with important haemodynamic significance and may play a key role in vascular biology and pathophysiology.     

A new approach to blood flow simulation in vascular networks

A proper analysis of blood flow is contingent upon accurate modelling of the branching pattern and vascular geometry of the network of interest. It is challenging to reconstruct the entire vascular network of any organ experimentally, in particular the pulmonary vasculature, because of its very high number of vessels, complexity of the branching pattern and poor accessibility in vivo. The objective of our research is to develop an innovative approach for the reconstruction of the full pulmonary vascular tree from available morphometric data. Our method consists of the use of morphometric data on those parts of the pulmonary vascular tree that are too small to reconstruct by medical imaging methods. This method is a three-step technique that reconstructs the entire pulmonary arterial tree down to the capillary bed. Vessels greater than 2 mm are reconstructed from direct volume and surface analysis using contrast-enhanced computed tomography. Vessels smaller than 2 mm are reconstructed from available morphometric and distensibility data and rearranged by applying Murray's laws. Implementation of morphometric data to reconstruct the branching pattern and applying Murray's laws to every vessel bifurcation simultaneously leads to an accurate vascular tree reconstruction. The reconstruction algorithm generates full arterial tree topography down to the ?rst capillary bifurcation. Geometry of each order of the vascular tree is generated separately to minimize the construction and simulation time. The node-to-node connectivity along with the diameter and length of every vessel segment is established and order numbers, according to the diameter-de?ned Strahler system, are assigned. In conclusion, the present model provides a morphological foundation for future analysis of blood flow in the pulmonary circulation     

Heterogeneous mechanics of the mouse pulmonary arterial network

Individualized modeling and simulation of blood flow mechanics find applications in both animal research and patient care. Individual animal or patient models for blood vessel mechanics are based on combining measured vascular geometry with a fluid structure model coupling formulations describing dynamics of the fluid and mechanics of the wall. For example, one-dimensional fluid flow modeling requires a constitutive law relating vessel cross-sectional deformation to pressure in the lumen. To investigate means of identifying appropriate constitutive relationships, an automated segmentation algorithm was applied to micro-computerized tomography images from a mouse lung obtained at four different static pressures to identify the static pressure–radius relationship for four generations of vessels in the pulmonary arterial network. A shape-fitting function was parameterized for each vessel in the network to characterize the nonlinear and heterogeneous nature of vessel distensibility in the pulmonary arteries. These data on morphometric and mechanical properties were used to simulate pressure and flow velocity propagation in the network using one-dimensional representations of fluid and vessel wall mechanics. Moreover, wave intensity analysis was used to study effects of wall mechanics on generation and propagation of pressure wave reflections. Simulations were conducted to investigate the role of linear versus nonlinear formulations of wall elasticity and homogeneous versus heterogeneous treatments of vessel wall properties. Accounting for heterogeneity, by parameterizing the pressure/distention equation of state individually for each vessel segment, was found to have little effect on the predicted pressure profiles and wave propagation compared to a homogeneous parameterization based on average behavior. However, substantially different results were obtained using a linear elastic thin-shell model than were obtained using a nonlinear model that has a more physiologically realistic pressure versus radius relationship.     

Functional hierarchy of coronary circulation: direct evidence of a structure-function relation

The heart muscle is nourished by a complex system of blood vessels that make up the coronary circulation. Here we show that the design of the coronary circulation has a functional hierarchy. A full anatomic model of the coronary arterial tree, containing millions of blood vessels down to the capillary vessels, was simulated based on previously measured porcine morphometric data. A network analysis of blood flow through every vessel segment was carried out based on the laws of fluid mechanics and appropriate boundary conditions. Our results show an abrupt change in cross-sectional area that demarcates the transition from epicardial (EPCA) to intramyocardial (IMCA) coronary arteries. Furthermore, a similar pattern of blood flow was observed with a corresponding transition from EPCA to IMCA. These results suggest functional differences between the two types of vessels. An additional abrupt change occurs in the IMCA in relation to flow velocity. The velocity is fairly uniform proximal to these vessels but drops significantly distal to those vessels toward the capillary branches. This finding suggests functional differences between large and small IMCA. Collectively, these observations suggest a novel functional hierarchy of the coronary vascular tree and provide direct evidence of a structure-function relation.     

The response of the pulmonary circulation to exercise during normoxia and hypoxia following pneumonectomy in the adult sheep

Pneumonectomy approximately halves the available pulmonary vascular bed. It is unknown whether the remaining lung has sufficient vascular reserve to cope with increased blood flow under stressful conditions without demonstrating abnormal pulmonary hemodynamics. To investigate this question, unanesthetized ewes with vascular catheters had hemodynamics assessed before and after a left pneumonectomy. Subsequently, on different days, the sheep were exercised on a treadmill under normoxic and hypobaric hypoxic (430 mmHg) (1 mmHg = 133.3 Pa) conditions. Pneumonectomy itself increased mean pulmonary arterial pressure by 4 mmHg. During normoxic or hypoxic exercise, the pneumonectomized sheep demonstrated a pulmonary hemodynamic response similar to normal sheep with two lungs. The pressure-flow relation for the right lung suggested the vascular reserve of the lung was not exceeded during exercise in the pneumonectomized sheep. Eighteen to 70 days after pneumonectomy there was no evidence of right ventricular hypertrophy, but there were small increases in the number of muscularized vessels less than 50 microns diameter and in the amount of muscle in normally muscularized pulmonary arteries. This study demonstrates that pneumonectomy slightly increases mean pulmonary arterial pressure. However, there is sufficient vascular reserve in the remaining lung to permit a normal hemodynamic response to exercise-induced increased blood flow even under hypoxic conditions.     

Axial shift of erythrocytes in arteries supplying blood to the cerebral cortex

In experiments with rabbits the widths of the axial flows of erythrocytes and of the parietal plasma layers were assessed in pial arterial ramifications supplying the cerebral cortex after their in vivo and in situ fixation under conditions of control and vasodilatation. A strict proportional relationship was revealed between the width of red cell flows and the diameter of pial arteries of 15-200 microns wide. However, the relative plasma volume in the microvessels below 50 microns in diameter was comparatively greater than in the larger vessels. The obtained results prove the feasibility of assessing the microvessels' diameters in tissues where one can see the red cell flow but the vascular walls are invisible. One of the reasons for the lower hematocrit in smaller blood vessels as compared to the larger ones was also elucidated.     

Alterations in regional vascular geometry produced by theoretical stent implantation influence distributions of wall shear stress: analysis of a curved coronary artery using 3D computational fluid dynamics modeling

Background  

The success of stent implantation in the restoration of blood flow through areas of vascular narrowing is limited by restenosis. Several recent studies have suggested that the local geometric environment created by a deployed stent may influence regional blood flow characteristics and alter distributions of wall shear stress (WSS) after implantation, thereby rendering specific areas of the vessel wall more susceptible to neointimal hyperplasia and restenosis. Stents are most frequently implanted in curved vessels such as the coronary arteries, but most computational studies examining blood flow patterns through stented vessels conducted to date use linear, cylindrical geometric models. It appears highly probable that restenosis occurring after stent implantation in curved arteries also occurs as a consequence of changes in fluid dynamics that are established immediately after stent implantation.     

Development of the paravascular bed of the vessels of the human heart during the prenatal period of ontogenesis

The paravascular bed of the cardiac vessels has been studied in 128 human fetuses at the age of 3-9 lunar months. Anatomical and histological techniques have been used, morphometrical analysis has been carried out. The paravascular bed of the cardiac wall vessels begins to form from the vascular epicardial network and from the paraneural vessels in 5-month-old fetuses. The paravasal longitudinal tracts are the first to form (the venous ones preceed the arterial). During the seventh month the nutritive vessels and the intramural networks of the main cardiac arteries and veins develop. The formation of the paraarterial bed is connected with the vascular diameter and with thickness of the arterial walls. Certain regularities in development of the venous paravascular bed are defined. By the beginning of the 8th month there are all main components of the paravascular bed of the cardiac vessels.     

The effect of catecholamines on blood circulation in the liver

In acute experiments on dogs under nembutal anaesthesia the pressure and blood flow in the vessels supplying the liver have been recorded simultaneously with registration of the hepatic blood content changes. Catecholamines injected into liver vessels have been found to change significantly the liver circulation: adrenaline and noradrenaline evoke the constriction of intrahepatic vessels and decrease the blood content in the liver, realising through the alpha-adrenoreceptors activation, isadrin causes a weak vasodilatation by the activation of beta-adrenoreceptors. A selective inactivation of isadrin in the liver is shown. The density of alpha-adrenoreceptors distribution in the intrahepatic vessels is large enough and apparently some times exceeds the density of beta-adrenoreceptors. In 1/3 of dogs the beta-adrenoreceptors in the liver vascular bed are absent at all or present in arterial bed only.     

Localized increases in ovarian vascular permeability and leucocyte accumulation after induced ovulation in rabbits.

Colloidal carbon was injected i.v. in mature virgin rabbits at different times after induction of ovulation by human chorionic gonadotrophin (hCG, 100 iu) or mating. Before induction of ovulation, slight carbon leakage was observed in the inner vascular ring of the theca interna of antral follicles, but blood vessels in the other ovarian compartments were unstained. Between 4 and 10.5 h after hCG-treatment or mating, vascular leakage was most marked in the blood vessels of the interstitial gland and in the theca interna of antral follicles. Just before ovulation, carbon particles were observed between granulosa cells and some carbon was seeping into the follicular fluid of preruptured follicles. Vascular leakage was also observed over the follicle dome before rupture as well as at the dorsomedial junction between the mesovarium and the ovary. The blood vessels stained with carbon were 7-70 microns diameter, representing capillaries and postcapillary venules. About 6 h after hCG injection, an increased number of polymorphonuclear leucocytes migrated from the vessels of these ovarian compartments into the surrounding interstitial tissue. The number of leucocytes seen in the follicular wall and ovarian medulla increased markedly towards ovulation. During early corpus luteum formation, the number of leucocytes decreased markedly. The localized vascular changes seen after mating and hCG stimulation were similar to an inflammatory reaction and could form the basis for the formation of peritoneal exudate after ovulation in rabbits and periovulatory ascitic accumulation seen in the peritoneal cavity of women during the menstrual cycle.     

Vascular wall extracellular matrix proteins and vascular diseases

Extracellular matrix proteins form the basic structure of blood vessels. Along with providing basic structural support to blood vessels, matrix proteins interact with different sets of vascular cells via cell surface integrin or non-integrin receptors. Such interactions induce vascular cell de novo synthesis of new matrix proteins during blood vessel development or remodeling. Under pathological conditions, vascular matrix proteins undergo proteolytic processing, yielding bioactive fragments to influence vascular wall matrix remodeling. Vascular cells also produce alternatively spliced variants that induce vascular cell production of different matrix proteins to interrupt matrix homeostasis, leading to increased blood vessel stiffness; vascular cell migration, proliferation, or death; or vascular wall leakage and rupture. Destruction of vascular matrix proteins leads to vascular cell or blood-borne leukocyte accumulation, proliferation, and neointima formation within the vascular wall; blood vessels prone to uncontrolled enlargement during blood flow diastole; tortuous vein development; and neovascularization from existing pathological tissue microvessels. Here we summarize discoveries related to blood vessel matrix proteins within the past decade from basic and clinical studies in humans and animals — from expression to cross-linking, assembly, and degradation under physiological and vascular pathological conditions, including atherosclerosis, aortic aneurysms, varicose veins, and hypertension.     

"Sausage-string" appearance of arteries and arterioles can be caused by an instability of the blood vessel wall

Vascular damage induced by acute hypertension is preceded by a peculiar pattern where blood vessels show alternating regions of constrictions and dilations ("sausages on a string"). The pattern occurs in the smaller blood vessels, and it plays a central role in causing the vascular damage. A related vascular pattern has been observed in larger vessels from several organs during angiography. In the larger vessels the occurrence of the pattern does not appear to be related to acute hypertension. A unifying feature between the phenomenon in large and small vessels seems to be an increase in vascular wall tension. Despite much research, the mechanisms underlying the sausage pattern have remained unknown. Here we present an anisotropic model of the vessel wall and show that the sausage pattern can arise because of an instability of the vessel wall. The model reproduces many of the key features observed experimentally. Most importantly, it suggests that the "sausaging" phenomenon is neither caused by a mechanical failure of the vessel wall due to a high blood pressure nor is it due to standing pressure waves caused by the beating of the heart. Rather, it is the expression of a general instability phenomenon. Experimental data suggest that the structural changes induced by the instability may cause secondary damage to the wall of small arteries and arterioles in the form of endothelial hyperpermeability followed by local fibrinoid necrosis of the vascular wall.     

Influence of size of emboli on extravascular lung water

We examined the influence of the size of emboli on the vascular volume (QL) and extravascular volume (Qev) accessible to 3HOH during a single pass through an isolated dog lung lobe using the double indicator-dilution method with 125I-human serum albumin as the vascular indicator. As successively more beads of a given diameter (58, 548, or 3,175 microns) were introduced into a lung lobe, a linear relationship between QL and Qev was obtained as they both decreased. The slope of the graph of QL vs. Qev with progressive embolism was directly proportional to the bead diameter. This suggested an approach for estimating the total vascular volume in vessels smaller than the diameter of the beads before embolization, referred to as Qm. If it is assumed that most of the transvascular diffusional exchange of 3HOH occurs in vessels smaller than the smallest beads (mainly capillaries) and that vessel obstruction does not change the ratio of Qev to the perfused capillary volume, the slope of the plot of QL vs. Qev is an estimate of the fraction, Qm/QL, of the total vascular volume in vessels smaller than the bead diameter. In the dog lung lobes studied, Qm/QL was approximately 0.64 for 58-microns vessels, 0.75 for 548-microns vessels, and 0.82 for 3,175-microns vessels. The results suggest that, with occlusion of vessels greater than or equal to 58 microns, 3HOH does not diffuse significantly into unperfused regions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Compound Ex Vivo and In Silico Method for Hemodynamic Analysis of Stented Arteries

Hemodynamic factors such as low wall shear stress have been shown to influence endothelial healing and atherogenesis in stent-free vessels. However, in stented vessels, a reliable quantitative analysis of such relations has not been possible due to the lack of a suitable method for the accurate acquisition of blood flow. The objective of this work was to develop a method for the precise reconstruction of hemodynamics and quantification of wall shear stress in stented vessels. We have developed such a method that can be applied to vessels stented in or ex vivo and processed ex vivo. Here we stented the coronary arteries of ex vivo porcine hearts, performed vascular corrosion casting, acquired the vessel geometry using micro-computed tomography and reconstructed blood flow and shear stress using computational fluid dynamics. The method yields accurate local flow information through anatomic fidelity, capturing in detail the stent geometry, arterial tissue prolapse, radial and axial arterial deformation as well as strut malapposition. This novel compound method may serve as a unique tool for spatially resolved analysis of the relationship between hemodynamic factors and vascular biology. It can further be employed to optimize stent design and stenting strategies.     

The cytoarchitecture of the wall and the innervation pattern of the microvessels in the rat mammary gland: a scanning electron microscopic observation

This report describes the morphology of the smooth muscle cells, pericytes, and the perivascular autonomic nerve plexus of blood vessels in the rat mammary gland as visualized by scanning electron microscopy after removal of connective-tissue components. From the differences in cellular morphology, eight vascular segments were identified: 1) terminal arterioles (10-30 microns in outer diameter), with a compact layer of spindle-shaped and circularly oriented smooth muscle cells; 2) precapillary arterioles (6-12 microns), with a less compact layer of branched smooth muscle cells having circular processes; 3) arterial capillaries (4-7 microns), with " spidery " pericytes having mostly circularly oriented processes; 4) true capillaries (3-5 microns), with widely scattered pericytes having longitudinal and several circular processes; 5) venous capillaries (5-8 microns), with spidery pericytes having ramifying processes; 6) postcapillary venules (10-40 microns), with clustered spidery pericytes; 7) collecting venules (30-60 microns), with a discontinuous layer of circularly oriented and elongated stellate or branched spindle-shaped cells which may represent primitive smooth muscle cells; and 8) muscular venules (over 60 microns), with a discontinuous layer of ribbon-like smooth muscle cells having a series of small lateral projections. No focal precapillary sphincters were found. The nerve plexus appears to innervate terminal arterioles densely and precapillary arterioles less densely. Fine nerve fibers are only occasionally associated with arterial capillaries. Venous microvessels in the rat mammary gland seemingly lack innervation.     

Numerical simulation of aortic bifurcation flows: The effect of flow divider curvature

Two dimensional steady flow calculations in computational regions obtained from radiographs of human aortic bifurcations correlate well with unsteady measurements of wall shear in flow-through casts of the same vessels. The results suggest that wall slope may be an important factor affecting the variability of shear along the medial walls of this arterial segment. If extremes of shear stress promote atherogenesis, then variations in the curvature of the proximal iliac arteries may affect the susceptibility of these vessels to vascular disease on their medial aspect.     

Morphometry of the human pulmonary vasculature

Huang, W., R. T. Yen, M. McLaurine, and G. Bledsoe.Morphometry of the human pulmonary vasculature.J. Appl. Physiol. 81(5):2123-2133, 1996.The morphometric data on the branching patternand vascular geometry of the human pulmonary arterial and venous treesare presented. Arterial and venous casts were prepared by the siliconeelastomer casting method. Three recent innovations are used to describethe vascular geometry: the diameter-defined Strahler ordering model isused to assign branching orders, the connectivity matrix is used todescribe the connection of blood vessels from one order to another, anda distinction between vessel segments and vessel elements is used toexpress the series-parallel feature of the pulmonary vessels. A totalof 15 orders of arteries were found between the main pulmonary arteryand the capillaries in the left lung and a total of 15 orders of veinsbetween the capillaries and the left atrium in the right lung. Theelemental and segmental data are presented. The morphometric data arethen used to compute the total cross-sectional areas, blood volumes, and fractal dimensions in the pulmonary arterial and venous trees.

     

A framework for incorporating 3D hyperelastic vascular wall models in 1D blood flow simulations

We present a novel framework for investigating the role of vascular structure on arterial haemodynamics in large vessels, with a special focus on the human common carotid artery (CCA). The analysis is carried out by adopting a three-dimensional (3D) derived, fibre-reinforced, hyperelastic structural model, which is coupled with an axisymmetric, reduced order model describing blood flow. The vessel transmural pressure and lumen area are related via a Holzapfel–Ogden type of law, and the residual stresses along the thickness and length of the vessel are also accounted for. After a structural characterization of the adopted hyperelastic model, we investigate the link underlying the vascular wall response and blood-flow dynamics by comparing the proposed framework results against a popular tube law. The comparison shows that the behaviour of the model can be captured by the simpler linear surrogate only if a representative value of compliance is applied. Sobol’s multi-variable sensitivity analysis is then carried out in order to identify the extent to which the structural parameters have an impact on the CCA haemodynamics. In this case, the local pulse wave velocity (PWV) is used as index for representing the arterial transmission capacity of blood pressure waveforms. The sensitivity analysis suggests that some geometrical factors, such as the stress-free inner radius and opening angle, play a major role on the system’s haemodynamics. Subsequently, we quantified the differences in haemodynamic variables obtained from different virtual CCAs, tube laws and flow conditions. Although each artery presents a distinct vascular response, the differences obtained across different flow regimes are not significant. As expected, the linear tube law is unable to accurately capture all the haemodynamic features characterizing the current model. The findings from the sensitivity analysis are further confirmed by investigating the axial stretching effect on the CCA fluid dynamics. This factor does not seem to alter the pressure and flow waveforms. On the contrary, it is shown that, for an axially stretched vessel, the vascular wall exhibits an attenuation in absolute distension and an increase in circumferential stress, corroborating the findings of previous studies. This analysis shows that the new model offers a good balance between computational complexity and physics captured, making it an ideal framework for studies aiming to investigate the profound link between vascular mechanobiology and blood flow.