In silico analyses of blood flow and oxygen transport in human micro-veins and valves

BACKGROUND: Almost 95% of the venous valves are micron scale found in veins smaller than 300μm diameter. The fluid dynamics of blood flow and transport through these micro venous valves and their contribution to thrombosis is not yet well understood or characterized due to difficulty in making direct measurements in murine models. OBJECTIVE: The unique flow patterns that may arise in physiological and pathological non-actuating micro venous valves are predicted. METHODS: Computational fluid and transport simulations are used to model blood flow and oxygen gradients in a microfluidic vein. RESULTS: The model successfully recreates the typical non-Newtonian vortical flow within the valve cusps seen in preclinical experimental models and in clinic. The analysis further reveals variation in the vortex strengths due to temporal changes in blood flow. The cusp oxygen is typically low from the main lumen, and it is regulated by systemic venous flow. CONCLUSIONS: The analysis leads to a clinically-relevant hypothesis that micro venous valves may not create a hypoxic environment needed for endothelial inflammation, which is one of the main causes of thrombosis. However, incompetent micro venous valves are still locations for complex fluid dynamics of blood leading to low shear regions that may contribute to thrombosis through other pathways.

Investigations on physico-chemical properties of TSPCU nonwoven for application as prosthetic venous valve

Electrospinning is used for producing nonwovens for medical polymer-based implants, such as prosthetic valves or covered scaffolds. In this study, nonwovens for prosthetic venous valves are investigated regarding their morphology and mechanics in physiological medium. Spinning molds were developed based on previous venous valve leaflet designs, 3D printed in different sizes and covered with electrospun nonwovens. Samples were stored in a physiological 0.9% saline at 37°C to investigate the influence of fiber rearrangement and swelling in medium for several weeks. Two different nonwovens of thermoplastic silicone-based polycarbonaturethane (TSPCU) were compared. Tensile test results show that storage in medium has a relevant influence on the mechanical properties. SEM images of TSPCU show substantially increased fiber diameters after 8 days stored in medium. After detaching the valve leaflet nonwovens from the molds, shrinkage of the material of approximately 12% was detected. A suitable valve size could be identified for joining with the stent structure into an interventional prosthetic venous valve. The results demonstrate the influence of storage conditions on the morphological and mechanical properties of electrospun TSPCU nonwovens. For development and dimensioning of venous valve leaflets, this change in mechanical behavior and possible shrinkage of the material has to be considered.

Clinical Presentation of Varicose Veins

Varicose vein is one type of venous insufficiency that presents with any dilated, elongated, or tortuous veins caused by permanent loss of its valvular efficiency. Destruction of venous valves in the axial veins results in venous hypertension, reflux, and total dilatation, causing varicosities and transudation of fluid into subcutaneous tissue. The first documented reference of varicose veins was found as illustrations on Ebers Papyrus dated 1550 B.C. in Athens. Evidence of surgical intervention was found in the 1860s. However dramatic advances of varicose vein management occurred in the latter half of twentieth century. Varicose veins affect from 40 to 60% of women and 15 to 30% men. Multiple intrinsic and extrinsic factors including age, gender, pregnancy, weight, height, race, diet, bowel habits, occupation, posture, previous DVT, genetics, and climate are considered to be the predisposing factors for formation of varicose vein. Other reported factors are hereditary, standing occupation, chair sitting, tight underclothes, raised toilet seats, lack of exercise, smoking, and oral contraceptives. Common symptoms are unsightly visible veins, pain, aching, swelling, itching, skin changes, ulceration, thrombophlebitis, and bleeding. The signs of varicose vein disease are edema, varicose eczema or thrombophlebitis, ulcers (typically found over the medial malleolus), hemosiderin skin staining, lipodermatosclerosis (tapering of legs above ankles, an “inverted champagne bottle” appearance), and atrophie blanche. Varicose vein is classified according to CEAP classification, the components of which are clinical, etiological, anatomy, and pathophysiology. The revised CEAP classification was published on 2020 based on four principles which were preservation of the reproducibility of CEAP, compatibility with prior versions, evidence-based medicine, and practicality.

Persistent Right Venous Valve: Insights From Multimodality Imaging

Anatomic variants in the right atrium are under-recognized and under-reported phenomena in cardiac imaging. In the fetus, right atrium serves as a conduit for oxygenated blood to be delivered to the left heart bypassing the right ventricle and the nonfunctional lungs. The anatomy in the fetal right atrium is designed for such purposeful circulation. The right and left venous valves are prominent structures in the fetal heart that direct inferior vena caval flow towards the foramen ovale. These anatomic structures typically regress and the foramen ovale closes after birth. However, the venous valves can persist leading to a range of anatomic, physiological, and pathological consequences in the adult. We describe various presentations of persistent venous valves, focusing on the right venous valve in this illustrated multimodality imaging article.

Role of Panchvalkala Kwatha Dhawana Karma in the management of non-healing varicose ulcer – A case study

ABSTRACT Venous ulcers (varicose ulcers or stasis ulcers) are the wounds occurring due to inappropriate functioning of venous valves, commonly of legs. It is most common and serious chronic venous insufficiency complication. The overall incidence rate is 0.76% in men and 1.42% in women. When venous valve gets damaged, it prevents the backflow of blood, which causes pressure in the vein that leads to hypertension, which stretches the veins resulting in ulcer formation. If not treated properly, the ulcers may get infected leading to cellulitis or gangrene and eventually may need amputation of the part of limb. In Ayurvedic prospective, varicose ulcers can be correlated with ‘Siragata Dushta Vrana’. Acharya Sushruta has advocated the Shashthi upakrama 1 (60 procedures) for treating the dushta vrana, among which Dhawana/ Parishek2 become third upakrama/procedure that means parishek procedure is included in first top 3 procedures and is useful in infected and non-healing wounds. Patients with varicose ulcers was advised to take ‘Sukshma Triphala’ internally and ‘Panchavalkala Kwatha Dhawana’ over lower limb daily twice a day followed by cleaning and dressing of wound which proved very effective and the ulcer healed completely in 30 days.

A Review of Current Noninvasive Imaging Surveillance Practices for Deep Venous Arterialization Procedures

Venous arterialization is an increasingly common procedure performed in patients with critical limb-threatening ischemia (CLTI) where there are no open or percutaneous revascularization options. This study aims to review the imaging follow-up for venous arterialization described in the literature. A systematic review was performed on venous arterialization studies for CLTI using the PRISMA methodology. A literature search was performed on 5 databases from inception. We included all original studies, case reports, and reviews regarding venous arterialization for all pathologies. We excluded free standing abstracts, animal studies, other than lower extremity, and foreign language studies. Our search strategy yielded 23 studies that met inclusion criteria, with 16 studies reporting a specific value from at least one surveillance imaging methodology. Most studies used Duplex imaging (16 studies) and TCPo2 (9 studies). Only 9 studies provided any detail regarding the Duplex findings. One study used focal peak systolic velocity (PSV) gradient (PSV at the lesion in the graft divided by PSV in a proximal segment of the graft) above 2.5 as an indicator for flow-inhibiting venous valves or stenosis in the graft. Another study reported a turbulent flow pattern in the graft, elevating peak velocities to 100 to 200 cm/s throughout the bypass. Four studies reported flow volume measurement through the bypass or in pedal vein ranging from 40 to 437 mL/min. Seven studies reported a mean increase of 18.7 mmHg in TCPo2. Eighty-two percent of patients saw an improvement of TCPo2 in 2 studies. To date, no criteria have been identified that are predictive of the success or failure of deep vein arterialization. Venous arterialization is an increasingly common procedure in the “no-option” diabetic patient. Duplex imaging with TCPo2 offers the most appropriate means of surveillance; however, the literature is sparse with no guidance on normal or critical values.

RASA1-driven cellular export of collagen IV is required for the development of lymphovenous and venous valves in mice

ABSTRACTRASA1, a negative regulator of Ras-MAPK signaling, is essential for the development and maintenance of lymphatic vessel valves. However, whether RASA1 is required for the development and maintenance of lymphovenous valves (LVV) and venous valves (VV) is unknown. In this study, we show that induced disruption of Rasa1 in mouse embryos did not affect initial specification of LVV or central VV, but did affect their continued development. Similarly, a switch to expression of a catalytically inactive form of RASA1 resulted in impaired LVV and VV development. Blocked development of LVV was associated with accumulation of the basement membrane protein, collagen IV, in LVV-forming endothelial cells (EC), and could be partially or completely rescued by MAPK inhibitors and drugs that promote collagen IV folding. Disruption of Rasa1 in adult mice resulted in venous hypertension and impaired VV function that was associated with loss of EC from VV leaflets. In conclusion, RASA1 functions as a negative regulator of Ras signaling in EC that is necessary for EC export of collagen IV, thus permitting the development of LVV and the development and maintenance of VV.

Functional ultrasound imaging of the venous valve of the great saphenous vein in the area around the crosse using the novel vector flow technique

PURPOSE: The aim of our pilot study is to consider if the new flow presentation of the vector flow (V-flow) allows an assessment of the valve morphology of the crosses with respect to an insufficiency. MATERIAL AND METHODS: We performed a total of 50 investigations in which we documented a complete valve closure at the so called “crosse” at the valve of the large saphenous vein, a delayed valve closure or an incomplete valve closure with consecutive insufficiency at the crosse. The valve function of the crosse is crucial for the development of varicosis. For our study we recorded age and gender of the patients. One patient in the study was suffering from Covid19. For the examinations we used a 3–9 MHz probe and a high-end ultrasound device. The examination was performed in a lying position and under quiet conditions. Before examination we practiced inhalation and exhalation as well as “pressing” or coughing with the patients, which resulted in a physiological closure of the venous valves. To rule out thrombosis, we carried out compression sonography on the legs. During the examination we documented the B-scan, the Color-Coded Duplex Sonography, the HR-flow and the V-flow for 3 seconds at the estuary of the crosses and incorporated these parameters into our measurements. Via V-flow, vectors can be imaged by representing the flow of erythrocytes and visually indicate a possible insufficiency due to delayed or incomplete valve closure. RESULTS: 31 of 50 patients (age 19–81years) showed a complete valve closure of the crosses, three of them suffered from thrombosis. In eight of the 50 study participants (age 45–79 years) a delayed valve closure could be diagnosed by V-flow within 1–2 seconds. None of them had a thrombosis, but six of them suffered from cancer. In eleven patients we derived an incomplete valve closure with insufficiency (age 51–88 years). With reflux it took >2 seconds to close the valve. The patient with Covid19 also showed an incomplete valve closure with insufficiency. At the same time this patient showed a Covid19-associated deep vein thrombosis. Eight additional patients also had a thrombosis. Six of them suffered from cancer. Overall, the results were best visualized by V-Flow. CONCLUSION: The crosse as a significant venous structure can be well investigated by V-flow with respect to hemodynamic changes and a resulted reflux. Also associated changes close to the valve can be visualized well.