Calf pump activity influencing venous hemodynamics in the lower extremity.
ABSTRACT: Calf muscle pump is the motive force enhancing return of venous blood from the lower extremity to the heart. It causes displacement of venous blood in both vertical and horizontal directions, generates ambulatory pressure gradient between thigh and lower leg veins, and bidirectional streaming within calf perforators. Ambulatory pressure gradient triggers venous reflux in incompetent veins, which induces ambulatory venous hypertension in the lower leg and foot. Bidirectional flow in calf perforators enables quick pressure equalization between deep and superficial veins of the lower leg; the outward (into the superficial veins) oriented component of the bidirectional flow taking place during calf muscle contraction is no pathological reflux but a physiological centripetal flow streaming via great saphenous vein into the femoral vein. Calf perforators are communicating channels between both systems making them conjoined vessels; they are not involved in the generation of pathological hemodynamic situations, nor do they cause ambulatory venous hypertension. The real cause why recurrences develop has not as yet been cleared. Pressure gradient arising during calf pump activity between the femoral vein and the saphenous remnant after abolition of saphenous reflux triggers biophysical and biochemical events, which might induce recurrence. Thus, abolition of saphenous reflux removes the hemodynamic disturbance, but at the same time it generates precondition for reflux recurrence and for the comeback of the previous pathological situation; this chain of events has been called hemodynamic paradox.
Project description:A curious hemodynamic phenomenon emerging as a consequence of the treatment of varicose veins can offer a reasonable explanation why varicose vein and reflux recurrences occur tenaciously irrespective of the applied therapeutic procedure. Saphenous reflux is the most important hemodynamic factor in varicose vein disease: it is responsible for the hemodynamic disturbance, ambulatory venous hypertension, clinical symptoms, and chronic venous insufficiency. Abolition of saphenous reflux eliminates the hemodynamic disturbance and restores physiological hemodynamic and pressure conditions, but at the same time it unavoidably evokes a pressure difference between the femoral vein and the incompetent superficial veins in the thigh during calf pump activity. The pressure difference increases flow and enhances fluid shear stress on the endothelium in pre-existing minor communicating channels between the femoral vein and the saphenous system in the thigh, which triggers release of biochemical agents nitride oxide and vascular endothelial growth factor; the consequence is enlargement (vascular remodeling) of the communicating channels, and ultimately reflux recurrence. Hence, the abolition of saphenous reflux creates preconditions for the comeback of the previous pathological situation. This phenomenon-starting the same trouble while fixing the problem-has been called hemodynamic paradox; is explains why varicose vein and reflux recurrence can occur after any mode of therapy.
Project description:Suprapubic varicose veins are usually indicative of unilateral iliac vein occlusion and venous collateralisation. We report two cases of suprapubic varicose veins following pelvic vein embolisation and subsequent pregnancy; both presented without residual pelvic venous reflux or pelvic venous obstruction. In both cases, there was no significant flow in the suprapubic veins indicating that they were not acting as a collateral post-pregnancy. One patient had this venous abnormality treated successfully with TRansluminal Occlusion of Perforators, followed by foam sclerotherapy to the main part of the suprapubic vein. This patient has since completed the reminder of her lower limb varicose vein treatment. We suggest that pregnancy may have caused prolonged intermittent compression of the left common iliac vein, and that this, together with the physiological impact of previous embolisation procedures, obstructed venous drainage from the left leg resulting in collateral vein formation within the 9-month gestation period.
Project description:<b>Objectives</b>: To find an objective diagnostic tool for the superficial veins in legs. <b>Methods</b>: This study included 137 patients who underwent TRANCE-MRI from 2017 to 2020 (IRB: 202001570B0). Among them, 53 with unilateral leg venous diseases underwent a QFlow scan and were classified into the reflux and non-reflux groups according to the status of the great saphenous veins. <b>Results</b>: The QFlow, namely stroke volume (SV), forward flow volume (FFV), mean flux (MF), stroke distance (SD), and mean velocity (MV) measured in the external iliac, femoral, popliteal, and great saphenous vein (GSV). The SV, FFV, SD, MF, SD, and MV in the GSV (morbid/non-morbid limbs) demonstrated a favorable ability to discriminate reflux from non-reflux in the ROC curve. The SD in the GSV and GSV/PV ratio (<i>p</i> = 0.049 and 0.047/cutoff = 86 and 117.1) and the MV in the EIV/FV ratio, GSV, and GSV/PV ratio (<i>p</i> = 0.035, 0.034, and 0.025/cutoff = 100.9, 86.1, and 122.9) exhibited the ability to discriminate between reflux and non-reflux group. The SD, MV, and FFV have better ability to discriminate a reflux from non-reflux group than the SV and MF. <b>Conclusions</b>: QFlow may be used to verify the reflux of superficial veins in the legs. An increasing GSV/PV ratio is a hallmark of reflux of superficial veins in the legs.
Project description:Venous leg ulcers (VLUs) are an important health problem, and the size of ulcers often affects patient care, healing time, and quality of life. However, the risk factors associated with ulcer size have been rarely reported. The aim of this study was to establish the risk factors for the size of venous ulceration by analyzing the patient demographics and the results of duplex ultrasonography.This study was an in-patient population-based cross-sectional study conducted at a single center during the period from 2013 to 2017. Men and women aged >18 years, who consecutively presented to our hospital with VLU, were included. According to the size of the ulcer, patients were divided into two groups, those with ulcers≤2 cm and those with ulcers >2 cm. Demographic, anthropometric, and clinical data were collected. For the analysis, univariate and multivariate logistic regressions were used.A total of 232 patients with VLUs were admitted to our hospital from 2013 to 2017, including 117 patients (50.4%) with ulcer diameters ≤2 cm and 115 patients (49.6%) with ulcer diameters >2 cm. According to the results of the multivariate analysis, the ulcer duration (P = .001), the diameter of perforating veins (PVs) around the ulcers (P = .025), the reflux time of common femoral veins (CFVs) (P = .013), the reflux time of great saphenous veins (GSVs) (P = .021), and the reflux time of PVs around the ulcers (P = .001) were independent risk factors for VLUs.These findings provide evidence that the size of VLU was significantly related to the ulcer duration, the diameter of PV around the ulcers, the CFV reflux time, the GSV reflux time, and the PV reflux time.
Project description:<b>Objectives/Background</b>: With decreased patient downtime and reduction in health expenditures, endovascular treatments have become popular for the treatment of venous insufficiency. In this study, we assessed the outcomes of using radiofrequency ablation (RFA) and sclerotherapy for refluxing veins and incompetent perforators in a developing country. <b>Materials and Methods</b>: Subjects were selected from an ongoing registry from October 15, 2015 to April 5, 2018. Patients were followed up until 6 months. Pre- and post-procedural Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) scores were compared, and complications were documented and treated accordingly. <b>Results:</b> In total, 102 limbs (n=97) with 76 great saphenous veins (GSVs) and 26 small saphenous veins (SSVs) underwent RFA, with 79% undergoing concomitant sclerotherapy. Mean follow-up time was 188 days (±33.16). Moreover, 59% were males and 41% females. At the end of follow-up, 99% of the legs had complete occlusion. Pre- and post-procedural CEAP scores were 4.21±1.5 and 3.36±1.7, respectively (p-value <0.001). Endovenous heat-induced thrombosis (EHIT) types 1, 2, 3, and 4 were found in 8.8%, 3.9%, 1.9%, and 0% of the legs, respectively. Most common complications were pain and tenderness (51%), bruising (18%), and paresthesia (7%). <b>Conclusion</b>: RFA and sclerotherapy have proved to be safe and efficacious. Computed tomography (CT) venous mapping aids in delineating complex venous anatomy and in ruling out deep vein thrombosis (DVT) in cases with discrepancy on Doppler ultrasound. Strict compliance of procedural and post-procedural protocol can assure promising results and futuristic value.
Project description:OBJECTIVES:The distribution of venous pathology in stasis leg ulcers is unclear. The main reason for this uncertainty is the lack of objective diagnostic tools. To fill this gap, we assessed the effectiveness of triggered angiography non-contrast-enhanced (TRANCE)-magnetic resonance imaging (MRI) in determining the venous status of patients with stasis leg ulcers. METHODS:This prospective observational study included the data of 23 patients with stasis leg ulcers who underwent TRANCE-MRI between April 2017 and May 2020; the data were retrospectively analyzed. TRANCE MRI utilizes differences in vascular signal intensity during the cardiac cycle for subsequent image subtraction, providing not only a venogram but also an arteriogram without the use of contrast agents or radiation. RESULTS:TRANCE MRI revealed that the stasis leg ulcers of nine of the 23 patients could be attributed to valvular insufficiency and venous occlusion (including deep venous thrombosis [DVT], May-Thurner syndrome, and other external compression). Moreover, TRANCE MRI demonstrated no venous pathology in five patients (21.7%). We analyzed TRANCE MRI hemodynamic parameters, namely stroke volume, forward flow volume, backward flow volume, regurgitant fraction, absolute volume, mean flux, stroke distance, and mean velocity, in the external iliac vein, femoral vein, popliteal vein, and great saphenous vein (GSV) in three of the patients with valvular insufficiency and three of those with venous occlusion. We found that the mean velocity and stroke volume in the GSV was higher than that in the popliteal vein in all patients with venous valvular insufficiency. CONCLUSIONS:Stasis leg ulcers may have no underlying venous disease and could be confirmed by TRANCE-MRI. TRANCE MRI has good Interrater reliability between Duplex study in greater saphenous venous insufficiency. It also potentially surpasses existing diagnostic modalities in terms of distinguishable hemodynamic figures. Accordingly, TRANCE-MRI is a safe and useful tool for examining stasis leg ulcers and is extensively applied currently.
Project description:Saphenous veins used as arterial grafts are exposed to arterial levels of oxygen partial pressure (pO2), which are much greater than what they experience in their native environment. The object of this study is to determine the impact of exposing human saphenous veins to arterial pO2. Saphenous veins and left internal mammary arteries from consenting patients undergoing coronary artery bypass grafting were cultured ex vivo for 2 weeks in the presence of arterial or venous pO2 using an established organ culture model. Saphenous veins cultured with arterial pO2 developed intimal hyperplasia as evidenced by 2.8-fold greater intimal area and 5.8-fold increase in cell proliferation compared to those freshly isolated. Saphenous veins cultured at venous pO2 or internal mammary arteries cultured at arterial pO2 did not develop intimal hyperplasia. Intimal hyperplasia was accompanied by two markers of elevated reactive oxygen species (ROS): increased dihydroethidium associated fluorescence (4-fold, p<0.05) and increased levels of the lipid peroxidation product, 4-hydroxynonenal (10-fold, p<0.05). A functional role of the increased ROS saphenous veins exposed to arterial pO2 is suggested by the observation that chronic exposure to tiron, a ROS scavenger, during the two-week culture period, blocked intimal hyperplasia. Electron paramagnetic resonance based oximetry revealed that the pO2 in the wall of the vessel tracked that of the atmosphere with a ~30 mmHg offset, thus the cells in the vessel wall were directly exposed to variations in pO2. Monolayer cultures of smooth muscle cells isolated from saphenous veins exhibited increased proliferation when exposed to arterial pO2 relative to those cultured at venous pO2. This increased proliferation was blocked by tiron. Taken together, these data suggest that exposure of human SV to arterial pO2 stimulates IH via a ROS-dependent pathway.
Project description:Extracellular matrix remodelling has been implicated in a number of vascular conditions, including venous hypertension and varicose veins. However, to date, no systematic analysis of matrix remodelling in human veins has been performed.To understand the consequences of venous hypertension, normal and varicose veins were evaluated using proteomics approaches targeting the extracellular matrix. Varicose saphenous veins removed during phlebectomy and normal saphenous veins obtained during coronary artery bypass surgery were collected for proteomics analysis. Extracellular matrix proteins were enriched from venous tissues. The proteomics analysis revealed the presence of >150 extracellular matrix proteins, of which 48 had not been previously detected in venous tissue. Extracellular matrix remodelling in varicose veins was characterized by a loss of aggrecan and several small leucine-rich proteoglycans and a compensatory increase in collagen I and laminins. Gene expression analysis of the same tissues suggested that the remodelling process associated with venous hypertension predominantly occurs at the protein rather than the transcript level. The loss of aggrecan in varicose veins was paralleled by a reduced expression of aggrecanases. Chymase and tryptase ?1 were among the up-regulated proteases. The effect of these serine proteases on the venous extracellular matrix was further explored by incubating normal saphenous veins with recombinant enzymes. Proteomics analysis revealed extensive extracellular matrix degradation after digestion with tryptase ?1. In comparison, chymase was less potent and degraded predominantly basement membrane-associated proteins.The present proteomics study provides unprecedented insights into the expression and degradation of structural and regulatory components of the vascular extracellular matrix in varicosis.
Project description:Endothelial dysfunction contributes significantly to the development of vascular diseases. However, a therapy able to reduce this derangement still needs to be identified. We evaluated the effects of pharmacological inhibition of Rac1, a small GTPase protein promoting oxidative stress, in human endothelial dysfunction.We performed vascular reactivity studies to test the effects of NSC23766, a Rac1 inhibitor, on endothelium-dependent vasorelaxation of saphenous vein segments collected from 85 subjects who had undergone surgery for venous insufficiency and from 11 patients who had undergone peripheral vascular surgery. The endothelium-dependent vasorelaxation of the varicose segments of saphenous veins collected from patients with venous insufficiency was markedly impaired and was also significantly lower than that observed in control nonvaricose vein tracts from the same veins. Rac1 activity, reactive oxygen species levels, and reduced nicotine adenine dinucleotide phosphate (NADPH) oxidase activity were significantly increased in varicose veins, and NSC23766 was able to significantly improve endothelium-dependent vasorelaxation of dysfunctional saphenous vein portions in a nitric oxide-dependent manner. These effects were paralleled by a significant reduction of NADPH oxidase activity and activation of endothelial nitric oxide synthase. Finally, we further corroborated this data by demonstrating that Rac1 inhibition significantly improves venous endothelial function and reduces NADPH oxidase activity in saphenous vein grafts harvested from patients with vascular diseases undergoing peripheral bypass surgery.Rac1 pharmacological inhibition rescues endothelial function and reduces oxidative stress in dysfunctional veins. Rac1 inhibition may represent a potential therapeutic intervention to reduce human endothelial dysfunction and subsequently vascular diseases in various clinical settings.
Project description:Imaging characteristics of stasis leg ulcers (SLUs) are not easily demonstrated through existing diagnostic tools. Early diagnosis and treatment are crucial. This pilot study was conducted to assess the quantitative flow (QFlow) in triggered angiography noncontrast enhanced (TRANCE) magnetic resonance imaging (MRI) to identify the hemodynamics of victims with stasis leg ulcers (SLUs). This study included 33 patients with SLUs and 14 healthy controls (HC). The 33 patients with SLUs were divided into a reflux (15 patients) and a nonreflux group (18 patients). QFlow was done in the reflux, the nonreflux, and the HC. The stroke volume (SV), forward flow volume (FFV), absolute flow volume (AFV), mean flow (MF), and mean velocity (MV) were higher in the reflux than in the HC group in most segments, namely the external iliac vein (EIV), popliteal vein (PV), and great saphenous vein (GSV) (SV, <i>p</i> = 0.008; FFV, <i>p</i> = 0.008; absolute stroke volume (ASV), <i>p</i> = 0.008; MF, <i>p</i> = 0.002; MV, <i>p</i> = 0.009). No differences in the QFlow patterns were found in the GSV segment between the nonreflux group and the HC. Excellent performance in discriminating SLU with superficial venous reflux was reported for SV in the EIV and the PV (area under the curve (AUC) = 0.851 and 0.872), FFV in the EIV and PV (AUC = 0.854 and 0.869), ASV in the EIV and PV (AUC = 0.848 and 0.881), and MF in the EIV and PV (AUC = 0.866 and 0.868). The cutoff levels of SV/FFV/ASV/MF in the EIV/FV/PV/GSV for discriminating the SLU with superficial venous reflux were identified (<i>p</i> < 0.005). In conclusion, SLUs present different QFlow patterns by different etiology. The QFlow parameters of all vessel segments were higher in the morbid limbs of the reflux group than HC. The GSV segment of the nonreflux group displayed a pattern like the HC.