Frequency analysis of arterial pulse transmission in the cranial cavity]

The changes of intracranial and arterial pulse shape under functional loads (hypervolemia and intracranial hypertension) were compared. The logarithmic amplitude-frequency characteristics were found and used for the synthesis of equivalent electrical circuit of arterial pressure pulses transmission on cerebrospinal fluid (CSF) in the cranial cavity. The model obtained points to the necessity of taking into account the induction which was not performed in the earlier models of the CSF-system. It is found that the attenuation factor permitted to estimate the stability of the intracranial circulation system to input influences under different functional conditions.     

Nonsymmetrical bifurcations in arterial branching

The results of optimality studies of the branching angles of arterial bifurcations are extended to nonsymmetrical bifurcations. Predicted nonsymmetrical bifurcations are found to be not unlike those observed in the cardiovascular system.     

Optimality principles in arterial branching

A comparative study of four optimality principles for the branching geometry of blood arteries is presented. The results offer four different criteria which can be tested by experimental data to establish which of these principles is followed in the cardiovascular system. More significantly, the results suggest the further possibility that the geometry of arterial junctions may be governed by all of these principles simultaneously, to thus achieve a much higher degree of optimality than has hitherto been suspected. This result offers a basis for seeking a correlation between the degree of optimality of a particular junction and the incidence of certain arterial lesions at that junction.     

Three-dimensional aspects of arterial branching

Arterial junctions give rise to different images when viewed from different directions. When a two-dimensional bifurcation is viewed in a direction other than normal to its branching plane, the branching angles will be distorted and the resulting picture will not be a true picture of that bifurcation. If the bifurcation is three-dimensional, some distortions will occur no matter which way the bifurcation is viewed. These distortions are analyzed for a wide range of situations and data is provided from which the corresponding errors can be estimated.     

Local geometry of arterial branching

A model of the geometrical structure of arterial bifurcations is proposed in the context of optimality of the bifurcation as a fluid conducting system. Optimality is considered both globally, in terms of the cardiovascular system as a whole, and locally, in terms of the orderliness of the flow in the bifurcation region. It is shown that a bifurcation can be optimal both globally and locally. Typical examples of such bifurcations are given.     

Electrical communication in branching arterial networks

Electrical communication and its role in blood flow regulation are built on an examination of charge movement in single, isolated vessels. How this process behaves in broader arterial networks remains unclear. This study examined the nature of electrical communication in arterial structures where vessel length and branching were varied. Analysis began with the deployment of an existing computational model expanded to form a variable range of vessel structures. Initial simulations revealed that focal endothelial stimulation generated electrical responses that conducted robustly along short unbranched vessels and to a lesser degree lengthened arteries or branching structures retaining a single branch point. These predictions matched functional observations from hamster mesenteric arteries and support the idea that an increased number of vascular cells attenuate conduction by augmenting electrical load. Expanding the virtual network to 31 branches revealed that electrical responses increasingly ascended from fifth- to first-order arteries when the number of stimulated distal vessels rose. This property enabled the vascular network to grade vasodilation and network perfusion as revealed through blood flow modeling. An elevation in endothelial-endothelial coupling resistance, akin to those in sepsis models, compromised this ascension of vasomotor/perfusion responses. A comparable change was not observed when the endothelium was focally disrupted to mimic disease states including atherosclerosis. In closing, this study highlights that vessel length and branching play a role in setting the conduction of electrical phenomenon along resistance arteries and within networks. It also emphasizes that modest changes in endothelial function can, under certain scenarios, impinge on network responsiveness and blood flow control.     

The role of shear forces in arterial branching

A new optimality principle for the branching angles of blood vessels in the cardiovascular system is proposed: the principle of minimum drag. The results are examined in the light of general observations and compared with those obtained from the principles of minimum work and minimum volume. It is shown that in some aspects the new principle is equally consistent with observations, and, in other aspects, it is perhaps more plausible than the other two principles.     

Cost of departure from optimality in arterial branching

Measurements of branching angles in the arterial tree have in the past indicated a great deal of scatter away from what is expected to be optimum on theoretical grounds. In this study the cost penalty of nonoptimum branching angles is calculated for the first time to determine how far from optimum these angles are. The results lead to the remarkable conclusion that while the scatter of the measured branching angles is fairly large, they represent deviations from optimum angles which correspond to only 2% or so penalty in cost.     

A computational investigation of the geometric factors affecting the severity of renal arterial stenoses

An arterial stenosis, or a constriction of an artery, can lead to higher pressure losses than those seen in a healthy artery which, in turn, can disrupt normal functioning of the body. Depending on the type, size, and location of a stenosis, the decision to intervene might be made. Because many arterial stenoses can be characterized by improved medical imaging, insights into the effects of stenosis geometry on pressure loss could provide important information for medical decision making. Computational fluid dynamics (CFD) provides a means of relatively quick investigation of various stenotic artery geometries. In this work, CFD simulations varying axial location of a stenosis, stenosis eccentricity, stenosis percent occlusion, and shape were performed. The simulated arteries were models of pathologic human renal arteries. The results indicate that pressure loss across a stenosis has no dependence on stenosis eccentricity. Pressure loss was shown not to be affected significantly by the axial location of the stenosis, but it was affected strongly by the stenosis structure. The most significant dependence was on percent stenosis; simulations indicated a critical percent stenosis of approximately 75–80%, above which pressure loss increases drastically. The critical percent stenosis identified here is consistent with guidelines used by physicians.     

Hydrodynamics of arterial branching--the effect of arterial branching on distal blood supply

A study was conducted to investigate the hydrodynamics of branching flow in relation to the blood supply to the basal part of the brain. A series of measurements of the branching loss-coefficients under laminar steady flow were conducted using model branches with various geometries, and the effect of branching on blood supply to distal areas was described using a lumped-parameter model of the vascular structure. It was revealed that in the blood circulation, branching loss is important where a small artery divides off with a large branching angle from a large trunk. It was also indicated that the effect of such branching on the distal blood supply might become more significant when the peripheral resistance is reduced, thereby increasing the blood velocity in the trunk.     

Selective regulation of arterial branching morphogenesis by synectin

Branching morphogenesis is a key process in the formation of vascular networks. To date, little is known regarding the molecular events regulating this process. We investigated the involvement of synectin in this process. In zebrafish embryos, synectin knockdown resulted in a hypoplastic dorsal aorta and hypobranched, stunted, and thin intersomitic vessels due to impaired migration and proliferation of angioblasts and arterial endothelial cells while not affecting venous development. Synectin(-/-) mice demonstrated decreased body and organ size, reduced numbers of arteries, and an altered pattern of arterial branching in multiple vascular beds while the venous system remained normal. Murine synectin(-/-) primary arterial, but not venous, endothelial cells showed decreased in vitro tube formation, migration, and proliferation and impaired polarization due to abnormal localization of activated Rac1. We conclude that synectin is involved in selective regulation of arterial, but not venous, growth and branching morphogenesis and that Rac1 plays an important role in this process.     

The branching angles in computer-generated optimized models of arterial trees

The structure of a complex arterial tree model is generated on the computer using the newly developed method of "constrained constructive optimization." The model tree is grown step by step, at each stage of development fulfilling invariant boundary conditions for pressures and flows. The development of structure is governed by adopting minimum volume inside the vessels as target function. The resulting model tree is analyzed regarding the relations between branching angles and segment radii. Results show good agreement with morphometric measurements on corrosion casts of human coronary arteries reported in the literature.     

A generalization of the optimal models of arterial branching

Optimal models of arterial branching angles are usually based on the assumption that the equation relating flow and radius is given byf=kr ³, as proposed by Murray in 1926. An exception is the model of Uylings (1977), in which he allowed the exponent ofr to vary from 2.33 to 3.0. Theoretical considerations coupled with empirical evidence suggest that the cubic flow equation may not be appropriate to describe the branching pattern of the arterial tree. The optimal models are modified to accommodate a more general flow equationf=kr ^x . Models that minimize a geometric feature such as surface or volume are sensitive to variations inx in a different way from those which minimize flow-related parameters, such as power loss due to friction and shear stress.     

Extracellular matrix and growth factors in branching morphogenesis

The unifying hypothesis of the NSCORT in gravitational biology postulates that the ECM and growth factors are key interrelated components of a macromolecular regulatory system. The ECM is known to be important in growth and branching morphogenesis of embryonic organs. Growth factors have been detected in the developing embryo, and often the pattern of localization is associated with areas undergoing epithelial-mesenchymal interactions. Causal relationships between these components may be of fundamental importance in control of branching morphogenesis.     

Comparison of steady and pulsatile flow in a double branching arterial model

Data are presented to compare fluid flow parameters for steady flow with those for time-varying flow in a simplified two branch model which simulates the region of the abdominal aorta near the celiac and superior mesenteric branches of the dog. Measurements in the model included laser doppler anemometry velocity profiles during steady flow, sinusoidal flow with a superimposed mean flow (referred to as simple oscillatory flow) and arterial pulsatile flow. Shear rate measurements were made by an electrochemical technique during steady flow. Flow visualization studies were done during steady and pulsatile flow. Fluid flow effects in the simplified model during steady flow showed many similarities to the results from previous steady flow studies in a canine aortic cast. Shear rates in the region of the proximal (first, or celiac) branch were independent of flow rates in the distal (second, or mesenteric) branch, but the shear pattern within the proximal branch changed significantly as flow in the proximal branch increased. Shear rates on the proximal flow divider (leading edge into the distal branch) depended primarily on the flow rate to the proximal branch, but not on flow to the distal branch. At certain daughter branch flow ratios (approximately 2:1, proximal to distal), flow separation was promoted at the outer wall of the second branch, but flow separation did not occur in the first branch. In contrast to the canine aortic case results, flow separation was never detected on the distal (mesenteric) flow divider of the simplified model. This observation reflects the subtle effects of geometry on flow since the mesenteric flow divider in the canine cast protrudes into the main flow whereas the distal flow divider in the simplified model does not. There were distinct differences in the flow phenomena between steady, simple oscillatory and arterial pulsatile flow. Peak shear rates during pulsatile flow were as much as 10--100 times greater than steady flow shear rates at comparable mean flow rates. Particularly noteworthy for the pulsatile flow with a Womersley parameter of sixteen were very blunt velocity profiles throughout systole, and the absence of flow separation or reversal in those regions of the model that exhibited flow separation during steady flow. The shape of the waveform influences the nature of the flow during time-varying flows. Future studies of fluid dynamics in model systems must consider the pulsatile nature of the flow if a true interpretation of arterial flow phenomena is to be made.     

R-Ras controls axon branching through afadin in cortical neurons

Regulation of axon growth, guidance, and branching is essential for constructing a correct neuronal network. R-Ras, a Ras-family small GTPase, has essential roles in axon formation and guidance. During axon formation, R-Ras activates a series of phosphatidylinositol 3-kinase signaling, inducing activation of a microtubule-assembly promoter-collapsin response mediator protein-2. However, signaling molecules linking R-Ras to actin cytoskeleton-regulating axonal morphology remain obscure. Here we identify afadin, an actin-binding protein harboring Ras association (RA) domains, as an effector of R-Ras inducing axon branching through F-actin reorganization. We observe endogenous interaction of afadin with R-Ras in cortical neurons during the stage of axonal development. Ectopic expression of afadin increases axon branch number, and the RA domains and the carboxyl-terminal F-actin binding domain are required for this action. RNA interference knockdown experiments reveal that knockdown of endogenous afadin suppressed both basal and R-Ras-mediated axon branching in cultured cortical neurons. Subcellular localization analysis shows that active R-Ras-induced translocation of afadin and its RA domains is responsible for afadin localizing to the membrane and inducing neurite development in Neuro2a cells. Overall, our findings demonstrate a novel signaling pathway downstream of R-Ras that controls axon branching.