Oscillatory flow of blood in a stenosed artery

In order to understand the abnormal flow conditions of blood in a locally constricted blood vessel, the analytical results are obtained for the oscillatory flow of blood which behaves as a Newtonian fluid. It is here assumed that the surface roughness is cosine-shaped and the maximum height of the roughness is very small compared with the radius of the unconstricted tube. Numerical solutions are presented for the instantaneous flow rate, resistive impedance, wall shear stress and phase lag.     

Flow-tissue interaction with compliance mismatch in a model stented artery

The insertion of an endovascular prosthesis is known to have a thrombogenic effect that is also a consequence of the interaction between the flowing blood and the stented arterial segment; in fact the prosthesis induces a compliance mismatch and a possible small expansion along the vessel that eventually gives rise to an anomalous distribution of wall shear stresses. The fluid dynamics inside a rectilinear elastic vessel with compliance and section variation is studied here numerically. A recently introduced perturbative approach is employed to model the interaction between the fluid and the elastic tissue; this approximate technique is first validated by comparison with a complete solution within a simple one-dimensional model of the same system. Then it is applied to an axisymmetric model in order to evaluate the flow dynamics and the distribution of wall shear stress in the stented vessel. Compliance mismatch is shown to produce more intense negative wall shear stresses in the stented segment while rapid variations of wall shear stress are found at the stent ends. These effects are enhanced when the prosthesis is accompanied by a small increase of the vessel lumen.     

Effect of blood flow on near-the-wall mass transport of drugs and other bioactive agents: a simple formula to estimate boundary layer concentrations

Transport of bioactive agents through the blood is essential for cardiovascular regulatory processes and drug delivery. Bioactive agents and other solutes infused into the blood through the wall of a blood vessel or released into the blood from an area in the vessel wall spread downstream of the infusion/release region and form a thin boundary layer in which solute concentration is higher than in the rest of the blood. Bioactive agents distributed along the vessel wall affect endothelial cells and regulate biological processes, such as thrombus formation, atherogenesis, and vascular remodeling. To calculate the concentration of solutes in the boundary layer, researchers have generally used numerical simulations. However, to investigate the effect of blood flow, infusion rate, and vessel geometry on the concentration of different solutes, many simulations are needed, leading to a time-consuming effort. In this paper, a relatively simple formula to quantify concentrations in a tube downstream of an infusion/release region is presented. Given known blood-flow rates, tube radius, solute diffusivity, and the length of the infusion region, this formula can be used to quickly estimate solute concentrations when infusion rates are known or to estimate infusion rates when solute concentrations at a point downstream of the infusion region are known. The developed formula is based on boundary layer theory and physical principles. The formula is an approximate solution of the advection-diffusion equations in the boundary layer region when solute concentration is small (dilute solution), infusion rate is modeled as a mass flux, and there is no transport of solute through the wall or chemical reactions downstream of the infusion region. Wall concentrations calculated using the formula developed in this paper were compared to the results from finite element models. Agreement between the results was within 10%. The developed formula could be used in experimental procedures to evaluate drug efficacy, in the design of drug-eluting stents, and to calculate rates of release of bioactive substances at active surfaces using downstream concentration measurements. In addition to being simple and fast to use, the formula gives accurate quantifications of concentrations and infusion rates under steady-state and oscillatory flow conditions, and therefore can be used to estimate boundary layer concentrations under physiological conditions.     

Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection

Meningitis caused by infectious pathogens is associated with vessel damage and infarct formation, however the physiological cause is often unknown. Cryptococcus neoformans is a human fungal pathogen and causative agent of cryptococcal meningitis, where vascular events are observed in up to 30% of patients, predominantly in severe infection. Therefore, we aimed to investigate how infection may lead to vessel damage and associated pathogen dissemination using a zebrafish model that permitted noninvasive in vivo imaging. We find that cryptococcal cells become trapped within the vasculature (dependent on their size) and proliferate there resulting in vasodilation. Localised cryptococcal growth, originating from a small number of cryptococcal cells in the vasculature was associated with sites of dissemination and simultaneously with loss of blood vessel integrity. Using a cell-cell junction tension reporter we identified dissemination from intact blood vessels and where vessel rupture occurred. Finally, we manipulated blood vessel tension via cell junctions and found increased tension resulted in increased dissemination. Our data suggest that global vascular vasodilation occurs following infection, resulting in increased vessel tension which subsequently increases dissemination events, representing a positive feedback loop. Thus, we identify a mechanism for blood vessel damage during cryptococcal infection that may represent a cause of vascular damage and cortical infarction during cryptococcal meningitis.     

Vascular NK-1 receptor occurrence in normal and chronic painful Achilles and patellar tendons: studies on chemically unfixed as well as fixed specimens

It is not known as to whether the Achilles and patellar tendons contain neurokinin-1 (NK-1) receptors. This is a drawback when considering the fact that pain symptoms are frequent in these and as recent studies show that the pain symptoms might be cured via interference with blood vessel function. In the present study, the human Achilles and patellar tendons were examined concerning immunohistochemical expression of the NK-1 receptor. Chemically unfixed and fixed specimens, TRITC and PAP stainings and a battery of NK-1 receptor antibodies, including antibodies against the C-terminus and the N-terminal region, were utilized. NK-1 receptor immunoreaction could be detected in inner parts of the walls of large blood vessels and in the walls of small blood vessels. To some extent, NK-1 immunoreaction was also detectable in small nerve fascicles and in tenocytes. It was found to be of utmost importance to apply both chemically unfixed and fixed specimens. The use of chemically unfixed tissue was found advantageous in order to depict the immunoreactions in the blood vessel walls. The observations represent new findings and are of relevance as substance P (SP) is known to be of importance where neurogenic angiogenesis contributes to diseases and as SP on the whole has profound effects concerning blood vessel regulation.     

Vascular metabolic dissipation in Murray's law

The metabolic dissipation in Murray's minimum energy hypothesis includes only the blood metabolism. The metabolic dissipation of the vascular tree, however, should also include the metabolism of passive and active components of the vessel wall. In this study, we extend the metabolic dissipation to include blood metabolism, as well as passive and active components of the vessel wall. The analysis is extended to the entire vascular arterial tree rather than a single vessel as in Murray's formulation. The calculations are based on experimentally measured morphological data of coronary artery network and the longitudinal distribution of blood pressure along the tree. Whereas the model includes multiple dissipation sources, the total metabolic consumption of a complex vascular tree is found to remain approximately proportional to the cumulative arterial volume of the unit. This implies that the previously described scaling relations for the various morphological features (volume, length, diameter, and flow) remain unchanged under the generalized condition of metabolic requirements of blood and blood vessel wall.     

A study on the non-linear flow of blood through arteries

The pulsatile flow of blood through arteries is investigated in this paper by treating the blood vessel as a thin-walled anisotropic, non-linearly viscoelastic, incompressible circular cylindrical shell; nonlinearities of the flow of blood are also paid due consideration. The displacement components of the vessel wall are obtained from the equations of equilibrium which have been linearized by employing the principle of superimposition of a small deformation on a state of known finite deformation. The influence of the wall deformation on the flow properties of blood, has been accounted for by considering suitably formulated continuity conditions. A finitedifference scheme is employed for solving the flow equations together with the boundary and initial conditions by using the locally measured values of pressure and pressure gradient. Numerical results obtained for the velocity profile of blood flowing in a canine middle descending thoracic aorta have been presented through figures.     

Small molecule screen for compounds that affect vascular development in the zebrafish retina

Blood vessel formation in the vertebrate eye is a precisely regulated process. In the human retina, both an excess and a deficiency of blood vessels may lead to a loss of vision. To gain insight into the molecular basis of vessel formation in the vertebrate retina and to develop pharmacological means of manipulating this process in a living organism, we further characterized the embryonic zebrafish eye vasculature, and performed a small molecule screen for compounds that affect blood vessel morphogenesis. The screening of approximately 2000 compounds revealed four small molecules that at specific concentrations affect retinal vessel morphology but do not produce obvious changes in trunk vessels, or in the neuronal architecture of the retina. Of these, two induce a pronounced widening of vessel diameter without a substantial loss of vessel number, one compound produces a loss of retinal blood vessels accompanied by a mild increase of their diameter, and finally one other generates a severe loss of retinal vessels. This work demonstrates the utility of zebrafish as a screening tool for small molecules that affect eye vasculature and presents several compounds of potential therapeutic importance.     

Computational fluid dynamic studies of leukocyte adhesion effects on non-Newtonian blood flow through microvessels

The study of the effect of leukocyte adhesion on blood flow in small vessels is of primary interest to understand the resistance changes in venular microcirculation. Available computational fluid dynamic studies provide information on the effect of leukocyte adhesion when blood is considered as a homogeneous Newtonian fluid. In the present work we aim to understand the effect of leukocyte adhesion on the non-Newtonian Casson fluid flow of blood in small venules; the Casson model represents the effect of red blood cell aggregation. In our model the blood vessel is considered as a circular cylinder and the leukocyte is considered as a truncated spherical protrusion in the inner side of the blood vessel. The cases of single leukocyte adhesion and leukocyte pairs in positions aligned along the same side, and opposite sides of the vessel wall are considered. The Casson fluid parameters are chosen for cat blood and human blood and comparisons are made for the effects of leukocyte adhesion in both species. Numerical simulations demonstrated that for a Casson fluid with hematocrit of 0.4 and flow rate Q = 0.072 nl/s, a single leukocyte increases flow resistance by 5% in a 32 microns diameter and 100 microns long vessel. For a smaller vessel of 18 microns, the flow resistance increases by 15%.     

豚鼠小肠粘膜下层内神经节丛与血管的伴行现象

本文应用NADH黄递酶联合Karnovsky-Roots乙酰胆碱酯酶组化技术研究了豚鼠小肠粘膜下层铺片上神经节丛与血管的关系,结果发现,由肌层穿入粘膜下层的小动、静脉及其分支互相伴行,环绕肠壁;动、静脉两侧有大致平行走向的伴行神经节丛,并从伴行的神经节丛发出分支终止于动、静脉壁上以及连接动、静脉两侧的神经节丛之间有纤维束相连。这种伴行现象在小动、静脉起始段和第一级分支段最为明显。伴行的神经节多数呈长梭形,其长轴与血管长轴平行。在血管“人”字形分支处,可见到“人”字形神经节,常位于静脉叉内。上述结果提示,伴行的神经节丛可能调节粘膜下层和粘膜的血流,从而影响小肠的吸收功能。     

血管活动的个性化

机体内不同部位的血管功能活动均具有各自独特的性质,称为血管的个性,主要表现为不同器官或区域的血管对同一刺激的反应不尽相同,甚至截然相反。血管的这种生理学特征保证了血管能在不同部位与不同机能状态下作出不同反应,巧妙地完成血液循环系统的功能,满足机体不同部位的血供需要。血管活动的个性化是血管生理学中的一个重要问题,对这一问题的研究将有助于阐明血管活动的客观规律,对研究血管疾病的发生与发展也具有重要意义     

Estimation of light intensity distribution in a culture vessel

Distribution of photosynthetic photon flux density (PPFD) in a culture vessel was estimated using a sensor film for measuring the integrated solar radiation. A plantlet model whose leaves were constructed from sensor film was used to simulate a potato plantlet. The plantlet model was put into a culture vessel and, after exposure to culture conditions for 20 days, PPFD was estimated for each individual model leaf based on the degree of fading of the sensor film. The method was able to demonstrate the light intensity distribution patterns inside a small test tube under downward lighting conditions. This technique allows for the estimation of light intensity distribution patterns inside a small culture vessel, which was previously difficult to measure by conventional methods.     

Forces on a Wall-Bound Leukocyte in a Small Vessel Due to Red Cells in the Blood Stream

As part of the inflammation response, white blood cells (leukocytes) are well known to bind nearly statically to the vessel walls, where they must resist the force exerted by the flowing blood. This force is particularly difficult to estimate due to the particulate character of blood, especially in small vessels where the red blood cells must substantially deform to pass an adhered leukocyte. An efficient simulation tool with realistically flexible red blood cells is used to estimate these forces. At these length scales, it is found that the red cells significantly augment the streamwise forces that must be resisted by the binding. However, interactions with the red cells are also found to cause an average wall-directed force, which can be anticipated to enhance binding. These forces increase significantly as hematocrit values approach 25% and decrease significantly as the leukocyte is made flatter on the wall. For a tube hematocrit of 25% and a spherical protrusion with a diameter three-quarters that of the vessel, the average forces are increased by ∼40% and the local forces are more than double those estimated with an effective-viscosity-homogenized blood. Both the enhanced streamwise and wall-ward forces and their unsteady character are potentially important in regard to binding mechanisms.     

The effect of portal hypertension on the structure of the pancreas in rats during the early periods of the experiment]

The model of Hiari disease obtained by a 50% constriction of the rat's posterior portal vein under the diaphragm was used in order to study the response of different structures of the pancreas on the 1st, 3, 5, 7, 15th days of experiment. The arterial vessels were found to have fairly active responses to venous congestion. The greatest load in sustaining microcirculation falls to large arteries, so they are more subjected to dystrophies, the severeness of which is proportional to the thickness of the vessels walls. In later terms of the experiment smaller arterial vessels are involved. Within a month blood circulation in the organ deteriorates and there appear small hemorrhages. The venous congestion results in a change of the structure and secretion of the acinous and insular cells of the pancreas.     

Active Ion Transport Across Canine Blood Vessel Walls

Experiments giving evidence of active Na and Cl ion fluxes across large canine blood vessel walls (aorta, vena cava) in vitro have been presented. The information has been obtained using ion tracer techniques after Ussing and with diffusion cells of the Hogben type. The available data suggest that the membranes are satisfactorily oxygenated by the bathing solutions saturated with oxygen at atmospheric pressure. Evidence is offered which indicates that active ion transport does occur across the aorta and vena cava in in vitro experiments. Under the conditions of the experiment net Na and Cl flux takes place from intima to adventitia across the aorta, and from adventitia to intima across the vena cava at low measured potential differences. The possible relationships of derangement of active ion transport mechanisms, produced by electric currents and tissue injury potential differences, to intravascular thrombosis are alluded to. It would appear that sodium and chloride fluxes across large blood vessel walls in vitro occur at least in part as the result of metabolic processes and cannot be explained simply on the basis of diffusion across a semipermeable membrane.     

Analytical solutions for the specific activities of a traced substance within the component parts of a simulated kidney-ureter system

Two models for a kidney-ureter system are considered: one model of one vessel in which a traced substance, undergoing exchange between the vessel and an external compartment, is emptying into the ureter; the second model of two approximately parallel, identical vessels in which a traced substance, undergoing exchange between each vessel and an external compartment, is emptying into the ureter. A single impulsive input of label into a vessel is assumed. For mathematical simplicity, the major conditions imposed on each system are: (1) rapid mixing transverse to a vessel axis and no mixing longitudinal to a vessel axis within the plasma; (2) small variation of the specific activity within the plasma in the longitudinal direction to a vessel axis; (3) constant flow rate of urine into the ureter and (4) constant exchange coefficients, tubule flow velocity and traced substance concentrations within individual compartments.     

Theoretical study on flow-dependent concentration polarization of low density lipoproteins at the luminal surface of a straight artery

It is suspected that physical and fluid mechanical factors play important roles in the localization of atherosclerotic lesions and intimal hyperplasia in man by affecting the transport of cholesterol in flowing blood to arterial walls. Hence, we have studied theoretically the effects of various physical and fluid mechanical factors such as wall shear rate, diffusivity of low density lipoproteins (LDL), and filtration velocity of water at the vessel wall on surface concentration of LDL at an arterial wall by means of a computer simulation of convective and diffusive transport of LDL in flowing blood to the wall of a straight artery under conditions of a steady flow. It was found that under normal physiologic conditions prevailing in the human arterial system, due to the presence of a filtration flow of water at the vessel wall, flow-dependent concentration polarization (accumulation or depletion) of LDL occurs at a blood/endothelium boundary. The surface concentration of LDL at an arterial wall takes higher values than that in the bulk flow in that vessel, and it is affected by three major factors, that is, wall shear rate, gamma w, filtration velocity of water at the vessel wall, Vw, and the distance from the entrance of the artery, L. It increases with increasing Vw and L, and decreasing gamma w hence the flow rate. Thus, under certain circumstances, the surface concentration of LDL could rise locally to a value which is several times higher than that in the bulk flow, or drop locally to a value even lower than a critical concentration for the maintenance of normal functions and survival of cells forming the vessel wall. These results suggest the possibility that all the vascular phenomena such as the localization of atherosclerotic lesions and intimal hyperplasia, formation of cerebral aneurysms, and adaptive changes of lumen diameter and wall structure of arteries and veins to certain changes in hemodynamic conditions in the circulation are governed by this flow-dependent concentration polarization of LDL which carry cholesterol.     

Remodeling of the collagen fiber architecture due to compaction in small vessels under tissue engineered conditions

Mechanical loading protocols in tissue engineering (TE) aim to improve the deposition of a properly organized collagen fiber network. In addition to collagen remodeling, these conditioning protocols can result in tissue compaction. Tissue compaction is beneficial to tissue collagen alignment, yet it may lead to a loss of functionality of the TE construct due to changes in geometry after culture. Here, a mathematical model is presented to relate the changes in collagen architecture to the local compaction within a TE small blood vessel, assuming that under static conditions, compaction is the main factor responsible for collagen fiber organization. An existing structurally based model is extended to incorporate volumetric tissue compaction. Subsequently, the model is applied to describe the collagen architecture of TE constructs under either strain based or stress based stimulus functions. Our computations indicate that stress based simulations result in a helical collagen fiber distribution along the vessel wall. The helix pitch angle increases from a circumferential direction in the inner wall, over about 45 deg in the middle vessel layer, to a longitudinal direction in the outer wall. These results are consistent with experimental data from TE small diameter blood vessels. In addition, our results suggest a stress dependent remodeling of the collagen, suggesting that cell traction is responsible for collagen orientation. These findings may be of value to design improved mechanical conditioning protocols to optimize the collagen architecture in engineered tissues.     

Mathematical modeling of the response of a resistive vessel to pressure

The response of small arterial vessels to internal pressure makes an essential contribution to autoregulation in the vascular bed. It is believed that free cytosolic Ca²⁺ concentration plays a pivotal role in the regulation of smooth muscle contractility and hence of the vascular lumen. A simple mathematical model of blood flow in a resistive vessel is suggested. The model is based on the experimental data obtained for cerebral arteries, but may be used for any other resistive vessel. The model not only describes the regulation of the vascular lumen by transmural pressure but also shows realistic behavior of the vessel radius and cytosolic [Ca²⁺] at different rates of pressure change. Possible variations in the radius along the vessel due to the Bayliss effect are considered.