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1.
Adv Physiol Educ ; 44(2): 262-267, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32412381

ABSTRACT

Ultrasound imaging is being used increasingly to aid in the teaching of human physiology and anatomy. Here we describe how its use can be integrated into the teaching of concepts surrounding venous circulation, specifically 1) venous valves and the muscle pump, 2) the effects of hydrostatic pressure on venous pressure, and 3) central venous pressure. The imaging procedures described are relatively simple but add a dimension that helps deliver the teaching points clearly and is enjoyable for students. They also aid in the link of basic physiology to clinical aspects of venous circulatory physiology.


Subject(s)
Blood Pressure Determination , Models, Cardiovascular , Muscle, Skeletal/blood supply , Physiology/education , Students , Ultrasonography , Venous Pressure , Venous Valves/diagnostic imaging , Comprehension , Educational Measurement , Educational Status , Humans , Hydrostatic Pressure , Muscle Contraction , Venous Valves/physiology
2.
Biomed Res Int ; 2019: 3147439, 2019.
Article in English | MEDLINE | ID: mdl-31687386

ABSTRACT

The superficial veins of the forelimb show high variability, both in man and in other primates, regarding the number of main venous trunks, their course, as well as the origin and location of openings. The distinction between two venous systems-the superficial and deep was made based on the relation of specific venous channels to the deep fascia; both groups of veins anastomose to each other through perforators piercing the deep fascia. In our work, we paid special attention to the organization of the venous system within the forelimb of the Anubis baboon (Papio anubis), as well as communications between the superficial and deep venous system. The main aim of the study was a detailed examination of the location of venous valves and perforating veins in forelimb of Anubis baboon. In the Anubis baboon, we observed the absence of the basilic vein. The main vessel within the forelimb, in the superficial venous system, was a well-developed cephalic vein. In all the cases, the cephalic vein opened into the external jugular vein. Also, in all of the examined specimens, there was an additional anastomosis connecting the cephalic and external jugular vein, i.e., persistent jugulocephalic vein located anterior to the clavicle. The venous vessels in the Anubis baboon were arranged in two main layers: superficial and deep, with both systems being connected by perforators located at the level of the carpus and cubital fossa. The number of venous valves within the cephalic vein was greater on the forearm the same as the mean intervalvular distance.


Subject(s)
Forelimb/blood supply , Papio anubis/physiology , Veins/physiology , Venous Valves/physiology , Animals , Forearm/blood supply , Jugular Veins/physiology , Primates/physiology
3.
Int J Numer Method Biomed Eng ; 35(2): e3156, 2019 02.
Article in English | MEDLINE | ID: mdl-30226292

ABSTRACT

Venous valves are bicuspidal valves that ensure that blood in veins only flows back to the heart. To prevent retrograde blood flow, the two intraluminal leaflets meet in the center of the vein and occlude the vessel. In fluid-structure interaction (FSI) simulations of venous valves, the large structural displacements may lead to mesh deteriorations and entanglements, causing instabilities of the solver and, consequently, the numerical solution to diverge. In this paper, we propose an arbitrary Lagrangian-Eulerian (ALE) scheme for FSI simulations designed to solve these instabilities. A monolithic formulation for the FSI problem is considered, and due to the complexity of the operators, the exact Jacobian matrix is evaluated using automatic differentiation. The method relies on the introduction of a staggered in time velocity to improve stability, and on fictitious springs to model the contact force of the valve leaflets. Because the large structural displacements may compromise the quality of the fluid mesh as well, a smoother fluid displacement, obtained with the introduction of a scaling factor that measures the distance of a fluid element from the valve leaflet tip, guarantees that there are no mesh entanglements in the fluid domain. To further improve stability, a streamline upwind Petrov-Galerkin (SUPG) method is employed. The proposed ALE scheme is applied to a two-dimensional (2D) model of a venous valve. The presented simulations show that the proposed method deals well with the large structural displacements of the problem, allowing a reconstruction of the valve behavior in both the opening and closing phase.


Subject(s)
Models, Cardiovascular , Venous Valves/physiology , Algorithms , Computer Simulation , Elastic Modulus , Humans
4.
J Vasc Surg Venous Lymphat Disord ; 6(4): 517-522.e1, 2018 07.
Article in English | MEDLINE | ID: mdl-29909857

ABSTRACT

BACKGROUND: It has been shown that venous valves have pairing arrangements with specific relative orientation and spacing that contribute to helical flows. The studies to date have not quantified the hemodynamic impact of helical flow formation. A computational model allows various valve orientations and spacings to be studied to better understand the hemodynamic effect of valve pairing. METHODS: Simulations were performed for paired valves at physiologically relevant spacing and orientations to study the flow features and hemodynamics associated with valve pairing configurations. The wall shear stress (WSS), residence time, and pressure drop were evaluated for the various valve pairing cases. RESULTS: It was found that the WSS on the lumen flow side (front) of the leaflet is several times higher than on the valve pocket side (back). With orthogonal paired valves, the WSS at the critical back side is increased. Helical flow was clearly observed only with orthogonal valve pairing. The residence time was reduced to less than half (0.47 vs 1.16 seconds) in the orthogonal valve case compared with the parallel valve cases. The farther spaced valves (6 cm) had the highest residence time. CONCLUSIONS: This simulation study shows that helical flow in the veins of lower extremities is strongly dependent on the relative orientation and spacing of the valves. For optimal orientation (∼90 degrees) and spacing (∼4 cm), strong helical flow is seen, which enhances WSS and reduces the flow resistance and residence time. These findings demonstrate a structure-function relation that optimizes flow patterns in normal physiology, which can be compromised in venous valve disease. The results of this study provide valuable insights that improve the current understanding of blood flow patterns around venous valves and the design of future multiple paired prosthetic valves.


Subject(s)
Hemodynamics , Lower Extremity/blood supply , Venous Valves/physiology , Blood Flow Velocity , Computer Simulation , Humans , Models, Cardiovascular , Prosthesis Design , Prosthesis Implantation/instrumentation , Regional Blood Flow , Stress, Mechanical , Time Factors , Venous Insufficiency/physiopathology , Venous Insufficiency/surgery , Venous Pressure , Venous Valves/transplantation
5.
J Vasc Surg Venous Lymphat Disord ; 6(3): 347-350, 2018 05.
Article in English | MEDLINE | ID: mdl-29292113

ABSTRACT

OBJECTIVE: The spectrum of chronic venous disease (CVD) in adults is well documented, whereas there is a paucity of data published commenting on pediatric CVD. We previously identified that there is often venous reflux present in cases of pediatric lower extremity edema despite an alternative confirmed diagnosis. To further assess the clinical significance of this venous reflux, this study aimed to elicit venous parameters in healthy pediatric controls. METHODS: Healthy pediatric volunteers aged 5 to 17 years were recruited for venous reflux study. A comprehensive venous reflux study was performed with the patient standing. Vein diameter, patterns of valvular reflux, and accessory venous anatomy were examined in the deep and superficial venous systems. RESULTS: Eighteen children including 10 boys and 8 girls were studied. Five volunteers were aged 5 to 8 years, six volunteers were aged 9 to 12 years, and seven volunteers were aged 13 to 17 years. Great saphenous vein (GSV) diameter at the saphenofemoral junction significantly increased with age. Deep vein valve closure time (VCT) did not differ significantly between groups, whereas GSV VCT was significantly higher in the 9- to 12-year age group. Incidental venous insufficiency was identified in 60% of children aged 5 to 8 years (n = 3), 50% of children aged 9 to 12 years (n = 3), and 57% of children aged 13 to 17 years (n = 4). All superficial venous reflux was confined to the GSV; there were no cases of isolated deep venous reflux. Reflux was identified at multiple GSV stations in 60% of children. There was no significant difference in incompetent GSV VCT in comparing children with and without deep venous reflux. Accessory superficial veins were identified in 20% of children aged 5 to 8 years (n = 1), 50% of children aged 9 to 12 years (n = 3), and 43% of children aged 13 to 17 years (n = 3). The presence of an accessory saphenous vein was not associated with deep venous reflux in any patient, and only 29% of those with accessory saphenous venous anatomy had evidence of superficial venous (GSV) reflux. CONCLUSIONS: The GSV continues to grow in diameter through the teenage years. Incidental valvular incompetence and GSV reflux are common. The presence of accessory saphenous veins is similarly common and not associated with venous reflux. The clinical significance and natural history of this incidental venous reflux remain unclear. Future research should determine whether these changes seen in the pediatric age group lead to CVD during later years of life.


Subject(s)
Saphenous Vein/diagnostic imaging , Venous Insufficiency/diagnostic imaging , Adolescent , Aging/pathology , Child , Child, Preschool , Chronic Disease , Female , Humans , Male , Pilot Projects , Saphenous Vein/anatomy & histology , Saphenous Vein/growth & development , Ultrasonography, Doppler, Duplex/methods , Venous Insufficiency/physiopathology , Venous Valves/diagnostic imaging , Venous Valves/physiology
6.
J Mech Behav Biomed Mater ; 77: 594-599, 2018 01.
Article in English | MEDLINE | ID: mdl-29096125

ABSTRACT

Chronic venous disease is caused by chronic venous insufficiency (CVI), which results in significant symptoms such as venous ulcers, ankle eczema, leg swelling, etc. Venous valve incompetence is a major cause of CVI. When the valves of veins in the leg become incompetent (i.e., do not close properly), blood is able to flow backwards (i.e., reflux), which results in blood pooling in the lower extremities, distal venous hypertension, and CVI. Current clinical therapies, such as surgical venous valve reconstruction and bioprosthetic venous valve replacement, are highly invasive and only moderately successful. This is due, in part, to the scanty information available about venous valve leaflet structure and mechanical properties. To date, only one previous study by our research group has reported on the mechanical properties of venous valve leaflet tissue, and specifically in the case of jugular vein valves. In this study, we conducted equibiaxial tensile tests on bovine saphenous vein valve leaflet tissues to better understand their nonlinear, anisotropic mechanical behavior. By stretching the valvular tissues to 60% strain in both the circumferential and radial directions, we generated stress-strain curves for proximal (i.e., those closest to the heart) and distal (i.e., those furthest from the heart) valve leaflets. Histology and collagen assays were also conducted to study corresponding leaflet microstructures and the biochemical properties of the tissues. Results showed: (1) saphenous venous valve tissues possessed overall anisotropic properties. The tissues were stiffer in the circumferential direction than in the radial direction (p<0.01), and (2) saphenous venous valve tissues from the proximal end showed nonlinear isotropic mechanical properties, while those from the distal end showed nonlinear anisotropic mechanical properties. (3) Distal saphenous venous valve tissues appeared to be stiffer than proximal ones in the circumferential direction, p=0.04 (i.e., inter-valvular variability), and (4) the collagen concentration showed a decreasing trend from the proximal to the distal end. This study focuses on highly relevant animal (bovine) tissues to develop test protocols, establish biomechanical structure-function correlations, and to provide data critical to the design of clinical prosthetic venous valves. To the best of the author's knowledge, this is the first study reporting the biaxial mechanical properties of saphenous venous valve leaflet tissues and thus contributes toward refining our collective understanding of valvular tissue biomechanics.


Subject(s)
Materials Testing/methods , Saphenous Vein/physiology , Stress, Mechanical , Venous Valves/physiology , Animals , Anisotropy , Biomechanical Phenomena , Blood Vessel Prosthesis , Cattle , Collagen/chemistry , Elasticity , Female , Humans , Models, Cardiovascular , Pilot Projects , Venous Insufficiency/therapy , Viscosity
7.
J Mech Behav Biomed Mater ; 75: 50-57, 2017 11.
Article in English | MEDLINE | ID: mdl-28692845

ABSTRACT

Venous valve tissues, though used in vein reconstruction surgeries and bioprosthetic valves with moderate success, have not been extensively studied with respect to their structure. Their inherent anisotropic, non-linear behavior combined with severe diseases which affect veins, such as chronic venous insufficiency, warrant understanding the structure and material behavior of these tissues. Hence, before any bioprosthetic grafts may be used in place of tissues, it is of the utmost importance to understand the mechanical and structural properties of these tissues as this may lead to higher success rates for valve replacement surgeries. The longevity of the bioprosthetics may also increase if the manufactured grafts behave the same as native valves. Building on the scant information about the uniaxial and biaxial mechanical properties of jugular venous valves and wall tissues from previous studies, the current focus of our investigation lies in understanding the material behavior by establishing a phenomenological strain energy-based constitutive relation for the tissues. We used bovine veins to study the behavior of valve leaflet tissue and adjoining wall tissue (from the proximal and distal ends of the veins) under different biaxial testing protocols. We looked at the behavior of numerical partial derivatives of the strain energy to select a suitable functional form for the strain energy for wall and valve tissues. Using this strain energy descriptor, we determined the Cauchy stress and compared it with experimental results under additional sets of displacement-controlled biaxial testing protocols to find material specific model parameters by the Powell's method algorithm. Results show that whereas wall tissue strain energy can be explained using a polynomial non-linear function, the valve tissue, due to higher non-linearities, requires an exponential function. This study may provide useful information for the primary stages of bioprosthetic designs and replacement surgeries and may support future studies investigating structural models. It may also support the study of valvular diseases by providing a way to understand material properties and behavior and to form a continuum model when required for numerical analyses and computational simulations.


Subject(s)
Jugular Veins/physiology , Models, Cardiovascular , Venous Valves/physiology , Animals , Anisotropy , Cattle , Stress, Mechanical
8.
Biomech Model Mechanobiol ; 16(6): 1911-1923, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28631145

ABSTRACT

Venous valve incompetence has been implicated in diseases ranging from chronic venous insufficiency (CVI) to intracranial venous hypertension. However, while the mechanical properties of venous valve leaflet tissues are central to CVI biomechanics and mechanobiology, neither stress-strain curves nor tangent moduli have been reported. Here, equibiaxial tensile mechanical tests were conducted to assess the tangent modulus, strength and anisotropy of venous valve leaflet tissues from bovine jugular veins. Valvular tissues were stretched to 60% strain in both the circumferential and radial directions, and leaflet tissue stress-strain curves were generated for proximal and distal valves (i.e., valves closest and furthest from the right heart, respectively). Toward linking mechanical properties to leaflet microstructure and composition, Masson's trichrome and Verhoeff-Van Gieson staining and collagen assays were conducted. Results showed: (1) Proximal bovine jugular vein venous valves tended to be bicuspid (i.e., have two leaflets), while distal valves tended to be tricuspid; (2) leaflet tissues from proximal valves exhibited approximately threefold higher peak tangent moduli in the circumferential direction than in the orthogonal radial direction (i.e., proximal valve leaflet tissues were anisotropic; [Formula: see text]); (3) individual leaflets excised from the same valve apparatus appeared to exhibit different mechanical properties (i.e., intra-valve variability); and (4) leaflets from distal valves exhibited a trend of higher soluble collagen concentrations than proximal ones (i.e., inter-valve variability). To the best of the authors' knowledge, this is the first study reporting biaxial mechanical properties of venous valve leaflet tissues. These results provide a baseline for studying venous valve incompetence at the tissue level and a quantitative basis for prosthetic venous valve design.


Subject(s)
Jugular Veins/physiology , Venous Valves/physiology , Animals , Biomechanical Phenomena , Cattle , Collagen/metabolism , Elastic Modulus , Stress, Mechanical
9.
Med Biol Eng Comput ; 55(6): 991-999, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27663560

ABSTRACT

Understanding the hemodynamics surrounding the venous valve environment is of a great importance for prosthetic valves design. The present study aims to evaluate the effect of leaflets' stiffening process on the venous valve hemodynamics, valve's failure on the next proximal valve hemodynamics and valve's failure in a secondary daughter vein on the healthy valve hemodynamics in the main vein when both of these valves are distal to a venous junction. Fully coupled, two-way fluid-structure interaction computational models were developed and employed. The sinus pocket region experiences the lowest fluid shear stress, and the base region of the sinus side of the leaflet experiences the highest tissue stress. The leaflets' stiffening increases the tissue stress the valve is experiencing in a very low fluid shear region. A similar effect occurs with the proximal healthy valve as a consequence of the distal valve's failure and with the mother vein valve as a consequence of daughter vein valve's failure. Understanding the described mechanisms may be helpful for elucidating the venous valve stiffness-function relationship in nature, the reasons for a retrograde development of reflux and the relationship between venous valves located near venous junctions, and for designing better prosthetic valves and for improving their positioning.


Subject(s)
Venous Valves/physiology , Heart Valve Prosthesis , Hemodynamics/physiology , Humans , Models, Cardiovascular , Prosthesis Design/methods , Stress, Mechanical
10.
J Biomech ; 49(13): 2845-2853, 2016 09 06.
Article in English | MEDLINE | ID: mdl-27457428

ABSTRACT

Chronic venous disease is defined as dysfunction of the venous system caused by incompetent venous valves with or without a proximal venous obstruction. Assessing the severity of the disease is challenging, since venous function is determined by various interacting hemodynamic factors. Mathematical models can relate these factors using physical laws and can thereby aid understanding of venous (patho-)physiology. To eventually use a mathematical model to support clinical decision making, first the model sensitivity needs to be determined. Therefore, the aim of this study is to assess the sensitivity of the venous valve model outputs to the relevant input parameters. Using a 1D pulse wave propagation model of the tibial vein including a venous valve, valve dynamics under head up tilt are simulated. A variance-based sensitivity analysis is performed based on generalized polynomial chaos expansion. Taking a global approach, individual parameter importance on the valve dynamics as well as importance of their interactions is determined. For the output related to opening state of the valve, the opening/closing pressure drop (dpvalve,0) is found to be the most important parameter. The venous radius (rvein,0) is related to venous filling volume and is consequently most important for the output describing venous filling time. Finally, it is concluded that improved assessment of rvein,0 and dpvalve,0 is most rewarding when simulating valve dynamics, as this results in the largest reduction in output uncertainty. In practice, this could be achieved using ultrasound imaging of the veins and fluid structure interaction simulations to characterize detailed valve dynamics, respectively.


Subject(s)
Hemodynamics , Models, Cardiovascular , Venous Valves/physiology , Tibia/blood supply
11.
J Vasc Surg Venous Lymphat Disord ; 4(3): 329-35, 2016 07.
Article in English | MEDLINE | ID: mdl-27318053

ABSTRACT

OBJECTIVE: Venous thromboembolism frequently results in thrombi formation near or within the pocket of a venous valve due to recirculating hemodynamics, which has been largely attributed to hypoxia-induced tissue factor (TF) expression. Numerical models are now capable of assessing the spatiotemporal behavior of the TF-initiated coagulation cascade under nonuniform hemodynamics. The aim of this study was to use such a numerical simulation to analyze the degree and location of thrombin formation with respect to TF position in the presence of disturbed flow induced by an open venous valve. METHODS: Thrombin formation was simulated using a computational model that captures the hemodynamics, kinetics, and chemical transport of 22 biochemical species. Disturbed flow is described by the presence of a valve in the equilibrium phase of the valve cycle with leaflets in a fully open position. Three different positions of TF downstream of the valve opening were investigated. RESULTS: The critical amount of TF required to initiate a thrombotic response is reduced by up to 80% when it is positioned underneath the recirculating regions near the valve opening. In addition, because of the increased surface area of the open valve cusp in conjunction with recirculating hemodynamics, it was observed that thrombin is generated inside the valve pocket even when the exposed region of TF is downstream of the valve. CONCLUSIONS: The presence of prothrombotic surface reactions in conjunction with recirculating hemodynamics provides an additional mechanism for thrombus formation in venous valves that does not require direct damage or dysfunction to the valve itself.


Subject(s)
Hemodynamics , Models, Cardiovascular , Thrombin/physiology , Thromboplastin/physiology , Venous Valves/physiology , Blood Coagulation , Computer Simulation , Humans
12.
Anat Histol Embryol ; 45(6): 409-417, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26412508

ABSTRACT

Dysfunction of venous valves can lead to hemodynamic disorders causing venous stasis, which would favour the occurrence of equine laminitis. However, very few studies have investigated venous valves in the horse digit. The purpose of this study was to compare valvular density between thoracic and pelvic limbs and to study the relationship between valvular density of veins and their location, diameter and wall thickness. After dissection, valvular density was calculated based on the number of valves counted in the principal veins of 7 thoracic and 7 pelvic limbs from 7 horses. Our results showed that the valvular density was higher in thoracic limbs, which probably reflects the adaptation to the consequences of hydrostatic pressure. The superficial veins have a higher valvular density that would prevent the varicose risk in the horse. The lower valvular density in the thick veins can be explained by the high density of the smooth muscular cells contained, which would cause an important vasoconstriction via the sympathetic nervous system. The veins with a large diameter also have a lower valvular density; these veins are not exposed to important changes in hydrostatic pressure. Other valvular characteristics may also be involved in the vascular disorders that may be related to the pathophysiology of laminitis.


Subject(s)
Forelimb/blood supply , Hindlimb/blood supply , Horse Diseases/pathology , Horses/anatomy & histology , Ischemia/veterinary , Venous Valves/physiology , Animals , Female , Hemodynamics/physiology , Hydrostatic Pressure , Ischemia/pathology , Male , Myocytes, Smooth Muscle/cytology , Vasoconstriction/physiology , Venous Valves/anatomy & histology
13.
Curr Neurovasc Res ; 12(4): 384-97, 2015.
Article in English | MEDLINE | ID: mdl-26256005

ABSTRACT

We quantify the effect of internal-jugular vein function on intracranial venous haemodynamics, with particular attention paid to venous reflux and intracranial venous hypertension. Haemodynamics in the head and neck is quantified by computing the velocity, flow and pressure fields, and vessel cross-sectional area in all major arteries and veins. For the computations we use a global, closed-loop multi-scale mathematical model for the entire human circulation, recently developed by the first two authors. Validation of the model against in vitro and in vivo Magnetic Resonance Imaging (MRI) measurements have been reported elsewhere. Here, the circulation model is equipped with a sub-model for venous valves. For the study, in addition to a healthy control, we identify two venous-valve related conditions, namely valve incompetence and valve obstruction. A parametric study for subjects in the supine position is carried out for nine cases. It is found that valve function has a visible effect on intracranial venous haemodynamics, including dural sinuses and deep cerebral veins. In particular, valve obstruction causes venous reflux, redirection of flow and intracranial venous hypertension. The clinical implications of the findings are unknown, though they may relate to recent hypotheses linking some neurological conditions to extra-cranial venous anomalies.


Subject(s)
Cerebrovascular Circulation/physiology , Hemodynamics/physiology , Intracranial Hypertension/physiopathology , Jugular Veins/physiology , Venous Valves/physiology , Blood Pressure/physiology , Computer Simulation , Humans , Magnetic Resonance Imaging , Models, Biological , Nervous System Diseases/physiopathology
14.
Eur J Vasc Endovasc Surg ; 48(1): 98-104, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24820915

ABSTRACT

BACKGROUND: The majority of bioprosthetic venous valves do not have a sinus pocket and, in practice, they are often placed in non-sinus segments of the veins. The aim of this study is to investigate the effect of the sinus pocket on the flow dynamics in a prosthetic valve. METHODS: A bench top in vitro experiment was set up at physiological flow conditions to simulate the flow inside a venous system. Bicuspid bioprosthetic valves with different leaflet lengths (5 and 10 mm) were tested in tubes with and without a sinus pocket and the flows around the valve were visualized by particle image velocimetry (PIV). Velocity data measurements were made and the vorticity was calculated in the with- and without-sinus set-ups. RESULTS: PIV measurements showed that vortex structure was maintained by the sinus. For the 10-mm leaflet length design with sinus, the jet width at the exit of the valve was 59% of that without sinus. For the 5-mm design with sinus, the jet width was 73% of the valve without sinus. Flow from the sinus region was entrained into the main jet observed near the exit of the sinus and altered the flow at the near wall region. CONCLUSIONS: The sinus pocket alters the flow around the valve and functions as flow regulator to smooth the flow pattern around the valve. The vortical structure inside the sinus is maintained at the valve leaflet tip during the valve cycle. For the prosthetic valve designated to be placed without a sinus, a shorter leaflet length is preferable and performs more closely to the valve with sinus.


Subject(s)
Bioprosthesis , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis , Hemorheology , Venous Valves/surgery , Blood Flow Velocity , Prosthesis Design , Venous Pressure , Venous Valves/physiology
15.
J Ultrasound Med ; 33(5): 803-9, 2014 May.
Article in English | MEDLINE | ID: mdl-24764335

ABSTRACT

OBJECTIVES: The purpose of this study was to determine the changes (if any) in the diameter and valve closure time of the lower limb veins in healthy young nulliparous women at different phases of the menstrual cycle. METHODS: Fifty-three young nulliparous women were asked to undergo clinical evaluations and duplex ultrasound examinations of both lower limb veins to monitor changes in the vein diameter and valve closure time at different phases of their menstrual cycles. The vein diameter on B-mode imaging and valve closure time on pulsed Doppler tracing were calculated at days 1 to 4, 14 to 16, and 25 to 28 of the menstrual cycle. Freidman and related samples Wilcoxon signed rank tests were used to determine time-related changes in venous function. RESULTS: The volunteers' mean age ± SD was 20.60 ± 1.90 years, and their mean body mass index was 23.90 ± 4.90 kg/m(2). There was a gradual increase in the vein diameter and valve closure time at the specified phases of the menstrual cycle. Friedman and related samples Wilcoxon signed rank tests for venous segment diameter and valve closure time changes between the different phases of the menstrual cycle were performed and showed statistical significance for each venous segment within each limb (P = .003-.025). Also, when adjusted for body mass index, statistical significance existed for the same venous segments in the same limbs (P =.001-.049). There was no statistical significance for the same venous segments at the same phase of the menstrual cycle between limbs (related samples Wilcoxon signed rank test: P =.079-.97). CONCLUSIONS: During the menstrual cycle, the lower limb veins show an increase in their diameter and valve closure time. These changes are probably mediated by the female sex hormones.


Subject(s)
Leg/blood supply , Leg/physiology , Menstrual Cycle/physiology , Ultrasonography, Doppler, Duplex/methods , Vascular Resistance/physiology , Venous Valves/diagnostic imaging , Venous Valves/physiology , Female , Humans , Leg/diagnostic imaging , Reproducibility of Results , Sensitivity and Specificity , Young Adult
16.
J Clin Invest ; 124(1): 273-84, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24292710

ABSTRACT

Mammals transport blood through a high-pressure, closed vascular network and lymph through a low-pressure, open vascular network. These vascular networks connect at the lymphovenous (LV) junction, where lymph drains into blood and an LV valve (LVV) prevents backflow of blood into lymphatic vessels. Here we describe an essential role for platelets in preventing blood from entering the lymphatic system at the LV junction. Loss of CLEC2, a receptor that activates platelets in response to lymphatic endothelial cells, resulted in backfilling of the lymphatic network with blood from the thoracic duct (TD) in both neonatal and mature mice. Fibrin-containing platelet thrombi were observed at the LVV and in the terminal TD in wild-type mice, but not Clec2-deficient mice. Analysis of mice lacking LVVs or lymphatic valves revealed that platelet-mediated thrombus formation limits LV backflow under conditions of impaired valve function. Examination of mice lacking integrin-mediated platelet aggregation indicated that platelet aggregation stabilizes thrombi that form in the lymphatic vascular environment to prevent retrograde blood flow. Collectively, these studies unveil a newly recognized form of hemostasis that functions with the LVV to safeguard the lymphatic vascular network throughout life.


Subject(s)
Blood Platelets/physiology , Hemostasis , Lymphatic Vessels/physiology , Aminopyridines , Animals , Fibrin/metabolism , Intestines/blood supply , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Intracellular Signaling Peptides and Proteins/metabolism , Lectins, C-Type/deficiency , Lectins, C-Type/genetics , Lymph Nodes/abnormalities , Mice , Mice, Knockout , Morpholines , Oxazines/pharmacology , Platelet Aggregation , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/metabolism , Pyridines/pharmacology , Pyrimidines , Regional Blood Flow , Syk Kinase , Thoracic Duct/blood supply , Thrombosis/physiopathology , Venous Valves/physiology
17.
Cell Mol Life Sci ; 70(6): 1055-66, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22922986

ABSTRACT

The efficient transport of blood and lymph relies on competent intraluminal valves that ensure unidirectional fluid flow through the vessels. In the lymphatic vessels, lack of luminal valves causes reflux of lymph and can lead to lymphedema, while dysfunction of venous valves is associated with venous hypertension, varicose veins, and thrombosis that can lead to edema and ulcerations. Despite their clinical importance, the mechanisms that regulate valve formation are poorly understood and have only recently begun to be characterized. Here, we discuss new findings regarding the development of venous and lymphatic valves that indicate the involvement of common molecular mechanisms in regulating valve formation in different vascular beds.


Subject(s)
Blood Vessels/physiology , Lymphatic Vessels/physiology , Models, Biological , Morphogenesis/physiology , Regional Blood Flow/physiology , Venous Valves/physiology , Blood Vessels/anatomy & histology , Cell Differentiation/physiology , Endothelial Cells , Humans , Lymphatic Vessels/anatomy & histology , Venous Valves/growth & development
18.
J Clin Invest ; 121(8): 2984-92, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21765212

ABSTRACT

Chronic venous disease and venous hypertension are common consequences of valve insufficiency, yet the molecular mechanisms regulating the formation and maintenance of venous valves have not been studied. Here, we provide what we believe to be the first description of venous valve morphogenesis and identify signaling pathways required for the process. The initial stages of valve development were found to involve induction of ephrin-B2, a key marker of arterial identity, by venous endothelial cells. Intriguingly, developing and mature venous valves also expressed a repertoire of proteins, including prospero-related homeobox 1 (Prox1), Vegfr3, and integrin-α9, previously characterized as specific and critical regulators of lymphangiogenesis. Using global and venous valve-selective knockout mice, we further demonstrate the requirement of ephrin-B2 and integrin-α9 signaling for the development and maintenance of venous valves. Our findings therefore identified molecular regulators of venous valve development and maintenance and highlighted the involvement of common morphogenetic processes and signaling pathways in controlling valve formation in veins and lymphatic vessels. Unexpectedly, we found that venous valve endothelial cells closely resemble lymphatic (valve) endothelia at the molecular level, suggesting plasticity in the ability of a terminally differentiated endothelial cell to take on a different phenotypic identity.


Subject(s)
Lymphangiogenesis/genetics , Lymphangiogenesis/physiology , Venous Valves/physiology , Animals , Disease Models, Animal , Endothelial Cells/cytology , Endothelium, Vascular/physiology , Ephrin-B2/metabolism , Fibronectins/metabolism , Humans , Hypertension/genetics , Integrin alpha Chains/metabolism , Mice , Mice, Transgenic , Models, Biological , Phenotype , Transgenes
20.
Rom J Morphol Embryol ; 51(1): 157-61, 2010.
Article in English | MEDLINE | ID: mdl-20191137

ABSTRACT

The valvular segment is a distinct venous structure, which, from a morphological point of view, is comprised of the following components: the valvular insertion, the valvular gorge entrance orifice, the valvular defile, the valvular gorge exit orifice, the valvular sinus. Endoscopic and echo Doppler examinations are used to identify the normal and the pathological morphology of the valvular segment, and the hemodynamic phenomena occurring at this level. Cusps' integrity and size as well as valvular dynamics are key elements directly involved in shaping the valvular segment in general, and the valvular sinus in particular. The valvular sinus shows an obvious hemodynamic determinism. Valvular segment pathology is the outcome either of a progressively long evolving process initialized by gravitational venous pressure overcharges, or of a rapidly evolving process such as the hemodynamic shock following intense physical efforts. Valvular defunctionalisation implies a different mechanism and a different type of cusp lesion.


Subject(s)
Lower Extremity/blood supply , Venous Valves/anatomy & histology , Venous Valves/pathology , Venous Valves/physiology , Endosonography , Hemodynamics , Humans , Lower Extremity/diagnostic imaging , Peripheral Vascular Diseases/diagnostic imaging , Peripheral Vascular Diseases/pathology , Peripheral Vascular Diseases/physiopathology , Ultrasonography, Doppler, Duplex , Venous Insufficiency/diagnostic imaging , Venous Insufficiency/pathology , Venous Insufficiency/physiopathology , Venous Valves/diagnostic imaging
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