Fluid dynamics of cerebrospinal venous flow in multiple sclerosis.

Stenotic immobile valves and other malformations obstruct normal cerebrospinal venous outflow, resulting in reflux flow which combines with the normal outflow to produce standing pressure waves in the internal jugular and other cerebrospinal veins. It is hypothesized that, if the cerebrospinal venous structure between the obstruction and the deep cerebral veins is sufficiently non-compliant, the standing wave will result in bidirectional flow in the fine cerebral veins. Bidirectional flow in the fine veins, over extended periods of time, will cause disorder in the veins' endothelial morphology, and ultimately, result in the disruption of the blood-brain barrier as observed in multiple sclerosis. This physics-based analysis demonstrates a positive correlation between clinically observed MS attributes with the predicted flow patterns and venous malformations that are based on fluid dynamics principles that include venous compliance influences. The physics-based approach used in this analysis provides new insights into MS pathologies based on predicted pressure and flow patterns.

Fluid dynamics of thoracic cavity venous flow in multiple sclerosis.

This paper hypothesizes, based on fluid dynamics principles, that in multiple sclerosis (MS) non-laminar, vortex blood flow occurs in the superior vena cava (SVC) and brachiocephalic veins (BVs), particularly at junctions with their tributary veins. The physics-based analysis demonstrates that the morphology and physical attributes of the major thoracic veins, and their tributary confluent veins, together with the attributes of the flowing blood, predict transition from laminar to non-laminar flow, primarily vortex flow, at select vein curvatures and junctions. Non-laminar, vortex flow results in the development of immobile stenotic valves and intraluminal flow obstructions, particularly in the internal jugular veins (IJVs) and in the azygos vein (AV) at their confluences with the SVC or BVs. Clinical trials' observations of vascular flow show that regions of low and reversing flow are associated with endothelial malformation. The physics-based analysis predicts the growth of intraluminal flaps and septa at segments of vein curvature and flow confluences. The analysis demonstrates positive correlations between predicted and clinically observed elongation of valve leaflets and between the predicted and observed prevalence of immobile valves at various venous flow confluences. The analysis predicts the formation of sclerotic plaques at venous junctions and curvatures, in locations that are analogous to plaques in atherosclerosis. The analysis predicts that increasing venous compliance increases the laminarity of venous flow and reduces the prevalence and severity of vein malformations and plaques, a potentially significant clinical result. An over-arching observation is that the correlations between predicted phenomena and clinically observed phenomena are sufficiently positive that the physics-based approach represents a new means for understanding the relationships between venous flow in MS and clinically observed venous malformations.

Effect of valve lesion on venous valve cycle: A modified immersed finite element modeling.

The present study aimed to understand the effect of venous valve lesion on the valve cycle. A modified immersed finite element method was used to model the blood-tissue interactions in the pathological vein. The contact process between leaflets or between leaflet and sinus was evaluated using an adhesive contact method. The venous valve modeling was validated by comparing the results of the healthy valve with those of experiments and other simulations. Four valve lesions induced by the abnormal elasticity variation were considered for the unhealthy valve: fibrosis, atrophy, incomplete fibrosis, and incomplete atrophy. The opening orifice area was inversely proportional to the structural stiffness of the valve, while the transvalvular flow velocity was proportional to the structural stiffness of the valve. The stiffening of the fibrotic leaflet led to a decrease in the orifice area and a stronger jet. The leaflet and blood wall shear stress (WSS) in fibrosis was the highest. The softening of the atrophic leaflet resulted in overly soft behavior. The venous incompetence and reflux were observed in atrophy. Also, the atrophic leaflet in incomplete atrophy exhibited weak resistance to the hemodynamic action, and the valve was reluctant to be closed owing to the large rotation of the healthy leaflet. Low blood WSS and maximum leaflet WSS existed in all the cases. A less biologically favorable condition was found especially in the fibrotic leaflet, involving a higher mechanical cost. This study provided an insight into the venous valve lesion, which might help understand the valve mechanism of the diseased vein. These findings will be more useful when the biology is also understood. Thus, more biological studies are needed.

Performance changes of venous valves following tissue treatment with novel in vitro system.

OBJECTIVES: The purpose of this study is to test venous valve performance and identify differences between native tissue and replacement devices developed with traditional tissue treatment methods using a new in vitro model with synchronized hemodynamic parameters and high-speed valve image acquisition. METHODS: An in vitro model mimicking the venous circulation to test valve performance was developed using hydrostatic pressure driven flow. Fresh and glutaraldehyde-treated vein segments were placed in the setup and opening/closing of the valves was captured by a high-speed camera. Hemodynamic data were obtained using synchronized hardware and virtual instrumentation. RESULTS: Geometric orifice area and opening/closing time of the valves was evaluated at the same hemodynamic conditions. A reduction in geometric orifice area of 27.2 ± 14.8% (p < 0.05) was observed following glutaraldehyde fixation. No significant difference in opening/closing time following chemical fixation was observed. CONCLUSIONS: The developed in vitro model was shown to be an effective method for measuring the performance of venous valves. The observed decrease in geometric orifice area following glutaraldehyde treatment indicates a decrease in flow through the valve, demonstrating the consequences of traditional tissue treatment methods.

[Possibilities of local phlebectomy in correction of pelvioperineal venous reflux]. / Vozmozhnosti lokal'noi flebéktomii v korrektsii pel'vio-perineal'nogo venoznogo refliuksa.

The work was based on the results of examination and treatment of 43 female patients presenting with varicose transformation of pelvic, perineal, and lower-limb veins. The inclusion criteria were as follows: the presence of visually determined varicose transformation of the veins of the external genital organs, perineum, posterior surface of the thighs, as well as valvular insufficiency of the mentioned veins by the findings of ultrasonographic angioscanning (USAS). The following exclusion criteria were applied: the presence of pregnancy, symptoms of pelvic venous plethora (PVP), and varicothrombophlebitis. In 33 women correction of the pelvioperineal reflux (PPR) was performed with the help of local phlebectomy on the large pudendal lips and perineum, with the maximally possible mobilization of the vessel within the limits of the operative wound. Miniphlebectomy with the use of Varady phleboextractors was performed in 10 women presenting with isolated varicose transformation of the subcutaneous veins of the posterior femoral surface. The duration of follow up of patients amounted to 3 years. The criteria for efficiency of the carried out treatment were as follows: freedom from varicose syndrome both in the perineum and on the lower extremities, as well as no PVP symptoms during the whole term of follow up. Varicose syndrome of the external genital organs, perineum and posterior surface of the femurs was successfully eliminated in 100% of patients. Meticulous mobilization and removal of the veins of the labia majora, perineum and subcutaneous femoral veins is a reliable method of removing pathological reflux of blood from the intrapelvic to superficial veins of the perineum and lower limbs. 100% of our patients were found to be free from relapses of either vulvar or perineal varicosity, with no evidence of lower limb varicose veins. Local phlebectomy is an efficient method of elimination of varicose syndrome induced by PVP in patients with dilatation of intrapelvic, vulvar and perineal veins.

[Functional assessment of primary lesion of the great saphenous vein when deciding upon stripping]. / Funktsional'naia otsenka pervichnogo porazheniia bol'shoi podkozhnoi veny pri reshenii voprosa o stripinge.

The purpose of the study was to examine a possibility of functional assessment of the great saphenous vein (GSV) with the help of a day orthostatic loading test for prognosis of restoration of the function of the GSV afterremoving its varicose tributaries in patients with primary varicose veins. Our prospective study included a total of sixty-five 29-to-53-year-old patients (15 men and 50 women, mean age - 36.7 years). The total number of the lower limb examined amounted to 87. All patients underwent ultrasonographic examination (duplex scanning) prior to operation, 1 and 12 months thereafter. The study was carried out using a day orthostatic loading test consisting in duplex scanning performed twice during 24 hours: in the evening after 18:00 hours and in the morning before 10:00 hours after a good night's rest. It was demonstrated that the day orthostatic loading test characterized the degree of preservation of the muscular-tonic properties of the GSV, making it possible to predict reversibility of reflux along it after removing the varicose tributaries, hence it may be used as a criterion for individualization of the choice of the scope of surgical intervention. A high orthostatic gradient prior to operation suggests preservation of the potential of the muscular-tonic function of the GSV; its decrease after surgery demonstrates reduction of the volemic loading on the GSV.

Platelets Drive Thrombus Propagation in a Hematocrit and Glycoprotein VI-Dependent Manner in an In Vitro Venous Thrombosis Model.

OBJECTIVE: The objective of this study was to measure the role of platelets and red blood cells on thrombus propagation in an in vitro model of venous valvular stasis. APPROACH AND RESULTS: A microfluidic model with dimensional similarity to human venous valves consists of a sinus distal to a sudden expansion, where for sufficiently high Reynolds numbers, 2 countercurrent vortices arise because of flow separation. The primary vortex is defined by the points of flow separation and reattachment. A secondary vortex forms in the deepest recess of the valve pocket characterized by low shear rates. An initial fibrin gel formed within the secondary vortex of a tissue factor-coated valve sinus. Platelets accumulated at the interface of the fibrin gel and the primary vortex. Red blood cells at physiological hematocrits were necessary to provide an adequate flux of platelets to support thrombus growth out of the valve sinus. A subpopulation of platelets that adhered to fibrin expose phosphatidylserine. Platelet-dependent thrombus growth was attenuated by inhibition of glycoprotein VI with a blocking Fab fragment or D-dimer. CONCLUSIONS: A 3-step process regulated by hemodynamics was necessary for robust thrombus propagation: First, immobilized tissue factor initiates coagulation and fibrin deposition within a low flow niche defined by a secondary vortex in the pocket of a model venous valve. Second, a primary vortex delivers platelets to the fibrin interface in a red blood cell-dependent manner. Third, platelets adhere to fibrin, activate through glycoprotein VI, express phosphatidylserine, and subsequently promote thrombus growth beyond the valve sinus and into the bulk flow.

Investigation of non-saphenous veins in C0S patients.

BACKGROUND: C0S patients have symptoms of chronic venous disorders (CVDs), though an anatomical or pathophysiological explanation is lacking. C0 and C1 classified lower limbs can present with valve incompetence from the second to sixth generation of tributaries of saphenous veins despite the absence of a detectable saphenous truncal reflux. We hypothesized that C0S venous symptoms could stem from the second to sixth generation of saphenous tributaries and small veins that are not connected to the saphenous system. The aim was to explore these veins in C0S subjects and compare them with asymptomatic C0A subjects. METHODS: This was an open, controlled study enrolling 36 subjects, where C0S patients (N.=18) were compared with asymptomatic C0A subjects (N.=18). The VAS (visual analog scale) was used to assess leg pain. Veins were assessed using B-flow ultrasound (valve anatomy), continuous-wave (CW) Doppler (flow patterns), biomicroscopy (visualization of nutritional vessels), laser Doppler flowmetry (quantify supine microvascular perfusion) and quantitative digital photo-plethysmography (PPG) (measuring post-exercise venous refilling time [VRT]). RESULTS: There were no significant differences between C0S and C0A subjects in terms of microvascular perfusion (laser-Doppler), nutritional vessels (biomicroscopy) and VRT (PPG). B-flow ultrasound was unable to acquire sufficient data in second generation saphenous tributaries. However, the CW Doppler identified two different flow patterns: uni- and bidirectional. Bidirectional flow was significantly (P=0.05) higher in C0S versus C0A patients. CONCLUSIONS: CW Doppler, using a flat high-sensitivity probe, revealed the presence of a bidirectional flow that was significantly (P=0.05) higher in C0S than in control patients, suggesting the presence of reflux in non axial veins. These data give a new perspective on the management of C0S patients.

Aging of the venous valves as a new risk factor for venous thrombosis in the elderly: the BATAVIA study.

Essentials Risk of venous thrombosis (VT) related to valve thickness and valvular reflux in unknown. Venous valves and reflux were measured by ultrasonography in cases and controls aged 70+. Risk of VT was associated with increased valve thickness and valvular reflux >1second. Thickening of valves is a generic process: there was no difference between right and left legs. SUMMARY: Background Increasing age is the strongest risk factor for venous thrombosis (VT). Increasing age has been related to a thickening of the venous valves and a decreased valvular function. The association between valve thickness and the risk of VT is not known. Objectives To assess the association between increased valve thickness and valve closure time (VCT) and the risk of VT. Methods Analyses were performed in the BATAVIA study, including 70 cases aged 70 + with a first VT and 96 controls. We performed an ultrasound examination of the valves in the popliteal veins. The valves were imaged with a 9 MHz linear probe using B-mode ultrasonography. VCT was measured as an indicator for valve function using an automatic inflatable cuff. To estimate the risk of VT, valve thickness was dichotomized at the 90th percentile as measured in controls and VCT was dichotomized at 1 s. Results Mean valve thickness of controls was similar in the left (0.36 mm, 95% CI 0.34-0.37) and right (0.36 mm, 95% CI 0.35-0.38) leg. In 45 cases a valve was observed in the contralateral leg with a mean valve thickness of 0.39 mm (95% CI 0.36-0.42). Cases had an increased valve thickness compared with controls: mean difference 0.028 mm (95%CI 0.001-0.055). Valve thickness > 90th percentile increased the risk of VT 2.9-fold. Mean VCT in controls was 0.38 s, in contralateral leg of cases 0.58 s. VCT > 1 s increased the risk of VT 2.8-fold (95% CI 0.8-10.4). Conclusions Risk of VT was associated with increased valve thickness and valvular reflux of > 1 s.

[Chronic venous diseases: valvular function and leukocyte-endothelial interaction, possibilities of pharmacotherapy]. / Khronicheskie zabolevaniia ven: funktsiia klapanov i leikotsitarno-éndotelial'noe vzaimodeistvie, vozmozhnosti farmakoterapii.

This article provides a review of the literature focusing on the data elucidating the pathogenesis of chronic venous diseases from the positions of macrohaemodynamic (venous valvular function) and microcirculatory impairments. Presented herein are confirmations of the interaction between two important mechanisms, as well as the literature data concerning the role of the venous microvalvular structures and possible haemodynamic impairments in functional venous insufficiency. Also presented are substantiations in confirmation of the theory of leukocyte-endothelial interaction, forming the basis for contemporary understanding of the pathogenesis of chronic venous diseases. This is followed by elucidating the role of venoactive drugs in conservative treatment of patients with chronic venous diseases, and, finally, touching upon current problems and promising approaches to solve them.

Modelling and simulation of flow and agglomeration in deep veins valves using discrete multi physics.

The hemodynamics in flexible deep veins valves is modelled by means of discrete multi-physics and an agglomeration algorithm is implemented to account for blood accrual in the flow. Computer simulations of a number of valves typologies are carried out. The results show that the rigidity and the length of the valve leaflets play a crucial role on both mechanical stress and stagnation in the flow. Rigid and short membranes may be inefficient in preventing blood reflux, but reduce the volume of stagnant blood potentially lowering the chances of thrombosis. Additionally, we also show that in venous valves, cell agglomeration is driven by stagnation rather than mechanical stress.

Role of vessel-to-prosthesis size mismatch in venous valve performance.

BACKGROUND: Efforts to treat chronic venous insufficiency have focused on the development of prosthetic venous valves. The role of prosthetic valve-to-vessel size matching has not been determined. The purpose of this investigation was to assess the effect of size mismatching on venous valve function and to establish a mismatch limit that affects valve hemodynamic performance and venous wall stress to improve future valve designs and implants. METHODS: Flow dynamics of prosthetic venous valves were studied in vitro using a pulse duplicator flow loop. Valve performance based on flow rate and pressure measurements was determined at oversizing ratios ranging from 4.2% to 25%. Valve open area ratios at different size mismatching ratios were investigated by image analysis. Finally, a wall stress analysis was used to determine the magnitude of circumferential (hoop) stress in the venous wall at various degrees of oversizing. RESULTS: Our findings indicate that valve regurgitate volume, closing time, and pressure difference across the valve are significantly elevated at mismatch ratios greater than ∼15%. This is supported by increases in regurgitate velocity and open area relative to valves tested at near-nominal diameters. At this degree of size mismatch, the wall stress is increased by a factor of two to three times relative to physiologic pressures. CONCLUSIONS: These findings establish a relationship between valve size matching and valve hemodynamic performance, including vessel wall stress, which should be considered in future valve implants. The size of the prosthetic valve should be within 15% of maximum vein size to optimize venous valve hemodynamic performance and to minimize the hoop wall stress.

After Superficial Ablation for Superficial Reflux Associated with Primary Deep Axial Reflux, Can Variable Outcomes be Caused by Deep Venous Valve Anomalies?

OBJECTIVE: To identify which deep anatomical anomalies can explain variable hemodynamic outcomes in patients with superficial reflux associated with primary deep axial reflux who underwent isolated superficial vein ablation without improvement. METHODS: This is a retrospective study of deep venous valve anomalies in patients who underwent superficial vein ablation for superficial and associated deep reflux. A group of 21 patients who were diagnosed with saphenous reflux associated with primary deep axial reflux, were submitted to great saphenous vein ablation. In 17 patients the deep reflux was not abolished. In this subgroup, surgical exploration of the deep valve was carried out using venotomy for possible valve repair. RESULTS: Among the 17 subgroup patients, four post-thrombotic lesions were discovered intra-operatively in four patients; they underwent different surgical procedures. In 13 of the subgroup patients, primary valve incompetence was confirmed intra-operatively. In 11 cases the leaflets were asymmetrical and in only two were they symmetrical. After valvuloplasty, deep reflux was abolished in all 13 patients. Clinical improvement was obtained in 12/13 patients (92%). It is noteworthy that abolition of deep reflux was associated with significant improvement in air plethysmography data as well as with improvement in clinical status measured on CEAP class, VCSS and the SF-36 questionnaire. CONCLUSION: Failure to correct deep axial reflux by superficial ablation in patients with superficial and associated primary deep axial reflux may be related to asymmetry in the leaflets of the incompetent deep venous valve.

[Free autovenous graft with destructed valves in treatment of severe ischemia of lower extremities]. / Lechenie kriticheskoi ishemii nizhnikh konechnostei s ispol'zovaniem svobodnogo autovenoznogo transplantata s razrushennymi klapanami.

AIM: to improve treatment of patients with severe atherosclerotic lesion of lower extremities arteries followed by critical ischemia by optimization of femoropopliteal bypass surgery. MATERIAL AND METHODS: Treament and survey of 60 patients with severe atherosclerotic lesion of femoropopliteotibial segment and critical lower limb ischemia were analyzed. Patients were divided into 2 groups depending on technique of femoropopliteal bypass. Conventional in situ autovenous technique was used in group 1. In the second group we used original method of free autovenous graft with destructed valves. RESULTS: Technique of free autovenous graft with destructed valves decreases incidence of early postoperative complications by 13.3%, remote thrombosis of graft by 13.3%. Also it increases physical and mental components of health by 7.9% and 3.1% respectively. CONCLUSION: Use of free autovenous graft with destructed valves is reasonable and improves results of treatment.

[Etiology, nomenclature and pathophysiology of chronic venous insufficiency]. / Ätiologie, Nomenklatur und Pathophysiologie der chronisch venösen Insuffizienz.

This article presents current notions and conceptions of the aetiopathogenesis of primary varicosis and chronic venous insufficiency, as well as an updated version of the nomenclature and terminology of venous disorders, which was recently agreed on in an international consensus conference. Furthermore, both CEAP-classification and venous severity score system are discussed.

Deep venous thrombosis: The valve cusp hypoxia thesis and its incompatibility with modern orthodoxy.

The valve cusp hypoxia thesis (VCHT) of the aetiology of deep venous thrombosis (DVT) was adumbrated in this journal in 1977 and fully articulated in 2008, the original hypothesis having been strongly corroborated by experiments published in 1981 and 1984. It presents a unitary account of the pathogenesis of venous thrombosis and embolism that is rooted in the pathophysiological tradition of Hunter, Virchow, Lister, Welch and Aschoff, a tradition traceable back to Harvey. In this paper we summarise the thesis in its mature form, consider its compatibility with recent advances in the DVT field, and ask why it has not yet been assimilated into the mainstream literature, which during the past half century has been dominated by a haematology-orientated 'consensus model'. We identify and discuss seven ways in which the VCHT is incompatible with these mainstream beliefs about the aetiology of venous thrombosis, drawing attention to: (1) the spurious nature of 'Virchow's triad'; (2) the crucial differences between 'venous thrombus' and 'clot'; the facts that (3) venous thrombi form in the valve pockets (VVPs), (4) DVT is not a primarily haematological condition, (5) the so-called 'thrombophilias' are not thrombogenic per se; (6) the conflict between the single unitary aetiology of DVT and the tacit assumption that the condition is 'multicausal'; (7) the inability of anticoagulants to prevent the initiation of venous thrombogenesis, though they do prevent the growth of thrombi to clinically significant size. In discussing point (7), we show that the VCHT indicates new approaches to mechanical prophylaxis against DVT. These approaches are then formulated as experimentally testable hypotheses, and we suggest methods for testing them preclinically using animal trials.

[Perforating veins insufficiency in patients with varicose disease].

MATERIAL AND METHODS: It was analyzed the results of complex survey and treatment of 181 patients with varicose disease CEAP degrees C3-C6. Ultrasonic scanning was applied to define localization, severity and extension of blood reflux in venous system. RESULTS: Superficial reflux was revealed in all patients, perforating--in 59.7%, deep--in 22.8% of cases. We concluded that high-intensive total-subtotal blood reflux in superficial veins was main hemodynamic factor resulted perforating insufficiency in 42% of patients, high-intensive deep reflux--in 17.7% of cases additionally. In patients with subcompensated course of disease superficial reflux removal and large perforating veins (diameter 4.5±0.5 mm) ligation are advisable. Small perforating veins insufficiency (diameter 3.5±0.5 mm) is eliminated independently after superficial reflux removal. Two-staged treatment should be used in patients with decompensated course of disease and trophic disorders ofshin. Perforating veins sclerotherapy under ultrasonic control is advisable secondarily after superficial reflux removal.

[Minimally invasive method of correction of valvular insufficiency of the femoral vein in various causes of its origin genesis].

Presented herein are the results of treatment of patients with chronic venous insufficiency and trophic ulcers of lower limbs on the background of varicose disease and postthrombophlebitic syndrome. The treatment consisted in removal of pathological deep vertical venous reflux by means of a modified method of dosed narrowing of the femoral vein according to P.G. Shvalb's technique [1]. The obtained outcomes confirmed the necessity of influencing the pathological vertical deep venous reflux in patients with severe forms of chronic venous insufficiency and pronounced retrograde shunt along deep veins.

Deep venous thrombosis and postthrombotic syndrome: invasive management.

Invasive management of postthrombotic syndrome encompasses the two ends of the deep vein thrombosis spectrum, patients with acute iliofemoral deep vein thrombosis and those with chronic postthrombotic iliofemoral venous obstruction. Of all patients with acute deep vein thrombosis, those with involvement of the iliofemoral segments have the most severe chronic postthrombotic morbidity. Catheter-based techniques now permit percutaneous treatment to eliminate thrombus, restore patency, potentially maintain valvular function, and improve quality of life. Randomized trial data support an initial treatment strategy of thrombus removal. Failure to eliminate acute thrombus from the iliofemoral system leads to chronic postthrombotic obstruction of venous outflow. Debilitating chronic postthrombotic symptoms of the long-standing obstruction of venous outflow can be reduced by restoring unobstructed venous drainage from the profunda femoris vein to the vena cava.