Can we predict and prevent the postthrombotic syndrome?

Postthrombotic syndrome (PTS) remains one of the major late complications of deep vein thrombosis (DVT) with a reported prevalence from 10 to 50%. Many factors were found to be related with the development and severity of PTS such as ipsilateral recurrent DVT, advanced age, obesity, ilio-femoral DVT and primary chronic venous disease presence. Some PTS prediction models have been proposed based on risk factor weight. However, it is still difficult to predict which patient with DVT will develop PTS and thus, the clinical application of these models remains limited. Among the identified problems the heterogeneity of the DVT patient population together with the variety of PTS clinical presentations and difficulties concerning PTS severity assessment should be mentioned. Difficulties on the implementation of the specific and objective PTS identification method have also the significant influence on the research focusing on PTS prevention modalities including risk factor modification, compression treatment, anticoagulation and invasive DVT treatment. In this review, the current approach and knowledge on PTS prediction and prevention are presented, including the conservative and invasive DVT treatment possibilities.

The risk of renal function deterioration in abdominal aortic stent graft patients with and without previous kidney function failure - an analysis of risk factors.

PURPOSE: Kidney failure influences the treatment outcomes of abdominal aortic aneurysm (AAA). A prospective study of renal function before and after aortic stent-graft treatment was performed. Special attention was paid to the influence of preoperative kidney function as well as the impact of the radiological follow-up. MATERIAL AND METHODS: A total of 214 endovascularly treated AAA patients were included. In all cases, pre- and postope-rative estimated glomerular filtration rate (eGFR) and serum creatinine were noted. Patients were prospectively followed up for a minimum of two years. RESULTS: The baseline eGFR was 69.38 ± 16.29 ml/min/1.73 m2. Chronic kidney disease at baseline was noted in 29% of patients. In the direct postoperative period, acute kidney injury was identified in 8.4% of cases. Additional endo-vascular procedures within two years of observation were performed in 5.6% of cases, and over the two years of follow-up, in the study group from one to six angio-computed tomographic scans (angio-CT) per patient were performed. The mean eGFR value after the 24-month follow-up was significantly lower than the preoperative value. Among the factors influencing kidney function, an angio-CT during the same hospital stay of the primary stent-graft procedures was identified. The type of stent-graft, contrast volume during the primary procedure, need for reintervention, concomitant disease presence, and statin use did not show statistical significance. CONCLUSIONS: Angio-CT followed by stent-graft implantation over a short time interval (within the same hospitalisation) significantly worsened renal function in the late follow-up and should be avoided in elective AAA cases.

Mechanical thrombectomy in acute stroke - Five years of experience in Poland.

OBJECTIVES: Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. METHODS AND RESULTS: We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. RESULTS: Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250±99min. 90.3% of the studied patients had MT within 6h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% - emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b-TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization - in 30.7%, mRS of 0-2 - in 31.4% and mRS of 6 in 22% of cases. CONCLUSION: Our results can help harmonize standards for MT in Poland according to international guidelines.

Superoxide dismutase 1 and glutathione peroxidase 1 are involved in the protective effect of sulodexide on vascular endothelial cells exposed to oxygen-glucose deprivation.

Sulodexide (SDX) is widely used in the treatment of both arterial and venous thrombotic disorders. In addition to its recognized antithrombotic action, SDX has endothelial protective potential, which is independent of the coagulation/fibrinolysis system. However, the detailed molecular mechanisms of the endothelioprotective action of the drug are still unresolved. The aim of the present study was to determine whether treatment with SDX at concentrations of 0.125-0.5 lipase releasing unit (LRU)/ml have on the expression and activity of antioxidant enzymes in ischemic endothelial cells and how these effects might be related to the antiapoptotic properties of SDX. In the present study, human umbilical vein endothelial cells (HUVECs) were subjected to ischemia-simulating conditions (combined oxygen and glucose deprivation, OGD) for 6h to determine the protective effects of SDX. SDX (0.25 and 0.5LRU/ml) in OGD significantly increased the cell viability and prevented mitochondrial depolarization in the HUVECs. Moreover, SDX protected the HUVECs against OGD-induced apoptosis. At concentrations of 0.25 and 0.5LRU/ml, the drug increased both superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPx1) mRNA/protein expression together with a significant attenuation of oxidative stress in ischemic HUVECs. Our findings also demonstrate that an increase in both SOD and GPx activity is involved in the protective effect of SDX on ischemic endothelial cells. Altogether, these results suggest that SDX has a positive effect on ischemia-induced endothelial damage because of its antioxidant and antiapoptotic properties.

Assessment of cerebral embolism and vascular reserve parameters in patients with carotid artery stenosis.

AIM: Carotid artery stenosis can result in the brain tissue injury related to the intracranial aterial flow disturbances as well as microembolic complications. The choice of the proper therapy in patients with carotid artery stenosis, especially asymptomatic, remains still a significant clinical problem. The study aim was an assessment of the cerebral embolism and brain vascular reserve parameters in patients with carotid artery stenosis regarding the occurrence of the clinical symptoms, the degree of stenosis as well as plaque morphology. METHODS: The study included 60 patients, with internal carotid artery stenosis. The degree of stenosis, the atherosclerotic plaque surface and morphology were assessed by the means of Duplex Doppler ultrasound. Cerebrovascular reactivity (vasomotor reactivity reserve test and Breath Holding Index) and monitoring of the microembolic signals (MES) were assessed with transcranial Doppler ultrasound examination (TCD). RESULTS: The vasoreactivity parameters were significantly lower in the group of patients with stenosis ≥70% and in patients with ulcerations on the plaque surface. Microembolic signals were recorded significantly more often in symptomatic patients; in patients with stenosis ≥70%; in patients with ulcerations on the plaque surface and those with hypoechogenic plaque structure. CONCLUSIONS: Microembolic signals in patients with symptomatic carotid stenosis are one of the ultrasound features of unstable carotid stenosis. Worse reactivity parameters of the cerebral arteries are associated with the presence of a large degree of carotid artery stenosis.

Complex interventional treatment in a patient with atrial fibrillation and stroke caused by large carotid artery thrombus: a case report.

BACKGROUND: The treatment option for acute ischaemic stroke depends on the duration of symptoms, the dynamics of neurological condition changes, the aetiology, type of stroke, as well as the results of angiographic and neuroimaging tests. CASE PRESENTATION: A 60-year-old male patient presented with progressive left hemisphere stroke caused by extensive cardiogenic embolism of the common carotid artery and a thrombus closing the internal carotid artery from its ostium to the level of its intracranial division. The complex revascularisation therapy involving surgical embolectomy of the common carotid artery, thrombectomy of the internal carotid artery and intra-arterial thrombolysis has led to the improvement of arterial patency and has countered the progression of acute cerebral ischaemia. CONCLUSION: Emergency carotid embolectomy together with thrombectomy and local thrombolytic rt-PA treatment may be a reasonable rescue therapy for carefully selected patients with large-vessel acute stroke. Further research is needed to establish the advantages and safety of surgical thrombectomy in patients with acute embolic occlusion of the carotid artery and ineffectiveness of or contraindications for systemic thrombolytic treatment.

Effects of Intermittent Pneumatic Compression on Reduction of Postoperative Lower Extremity Edema and Normalization of Foot Microcirculation Flow in Patients Undergoing Arterial Revascularization.

BACKGROUND In patients with chronic leg ischemia, the beneficial effect of arterial revascularization can be significantly decreased due to postoperative leg swelling. The aim of this study was to assess the effects of intermittent pneumatic compression (IPC) on skin flow normalization in patients undergoing revascularization procedures due to chronic leg ischemia. MATERIAL AND METHODS We evaluated 116 patients with chronic leg ischemia. The patients were divided into groups according to the performed treatment (endovascular or surgical) and implementation of IPC postoperatively. The leg edema assessment and microcirculation flow assessment were performed pre- and postoperatively, using percutaneous O2 pressure (TcpO2), cutaneous blood perfusion (CBP) measurements, and skin flow motion assessment. RESULTS In patients who did not receive IPC, a decrease in CBP value was observed in the 1st postoperative assessment. Among patients receiving IPC, the CBD value increased at the 1st and 2nd postoperative measurements, especially in the surgical group. The lowest TcpO2 values were observed in by-pass surgery group without IPC postoperatively. CONCLUSIONS The benefits of the by-pass procedure in patients with leg ischemia can be significantly reduced by postoperative edema. Among patients with postoperative leg edema, local tissue blood perfusion can be improved by the use of IPC, which can result in decreased local leg swelling, as well as improved skin blood perfusion and TcpO2.

[Astrocytes in ischemic stroke - a potential target for neuroprotective strategies]. / Astrocyty w udarze niedokrwiennym mózgu ­ potencjalny cel strategii neuroprotekcyjnych.

Ischemic stroke is one of the leading causes of adult death and disability worldwide. Present applied therapeutic strategies do not give satisfactory results. It is often emphasized that pharmacological actions aimed at reducing the area of ischemic brain injury should protect astrocytes forming together with neurons and the endothelium neurovascular unit. Astrocytes contribute importantly to proper neuronal function during both physiological and pathological conditions. In ischemic stroke, astrocytes are involved in regulation of water and ion homeostasis, cerebral blood flow, maintenance of the blood-brain barrier, and control of the extracellular level of glutamate, as well as being a source of neuroprotectants. On the other hand, astrocytes may also contribute to enlarged ischemic area due to their participation in inflammatory processes and production of potential neurotoxic substances. Herein we review experimental and clinical data concerning adaptive and pathological roles of astrocytes during both early and late phases of ischemia. Especially, we emphasize specific features of astrocytes that might become a potential target of therapeutic strategies for ischemic stroke.

A comparative clinical study on five types of compression therapy in patients with venous leg ulcers.

The aim of this study was to compare five types of compression therapy in venous leg ulcers (intermittent pneumatic vs. stockings vs. multi layer vs. two layer short stretch bandages vs. Unna boots). Primary study endpoints were analysis of changes of the total ulcer surface area, volume and linear dimensions inside observed groups. The secondary end points were comparisons between all groups the number of completely healed wounds (ulcer healing rates), Gilman index and percentage change of ulcer surface area. In total, 147 patients with unilateral venous leg ulcers were included to this study. Participants were randomly allocated to the groups: A, B, C, D and E. After two months the healing rate was the highest in group A (intermittent pneumatic compression) - 57.14%, 16/28 patients, B (ulcer stocking system) - 56.66%, 17/30 patients and C (multi layer short stretch bandage) - 58.62%, 17/29 patients. Significantly much worse rate found in group D (two layer short stretch bandages) - only 16.66%, 5/30 patients and E (Unna boots) - 20%, 6/30 patients. The analysis of changes of the percentage of Gilman index and wound total surface area confirmed that intermittent pneumatic compression, stockings and multi layer bandages are the most efficient. The two layer short - stretch bandages and Unna boots appeared again much less effective.

Changes of the serum properties and its effect on the endothelial cells restoration in patients with chronic disease treated with sulodexide.

OBJECTIVE: Inflammation and endothelial dysfunction are important venous changes in patients with chronic venous disease (CVD). The use of the venoactive drugs remains an important treatment modality for patients with CVD, reducing the severity of the CVD-related symptoms and swelling but also reducing inflammation and protecting endothelial cells. In this research, the effects of the serum obtained from patients with CVD before and after sulodexide treatment were evaluated for in vivo and in vitro inflammatory markers and endothelial cell function. METHODS: Inflammatory markers (IL-6, matrix metalloproteinase-9 [MMP-9], vascular cell adhesion molecule-1 [VCAM-1], and von Willebrand factor [vWF]) from the incompetent great saphenous veins (GSVs) and from the systemic venous circulation were studied in 10 patients with CVD (C2s) before and after 2 months of sulodexide (2 × 500 LSU/d) therapy. Serum from pretreatment and following sulodexide treated patients was evaluated for in vitro cultured human umbilical vein endothelial cell function. RESULTS: The serum collected from lower leg incompetent GSVs had significantly elevated levels of VCAM-1 (+29%, P < .001) compared with the serum from the systemic circulation. Endothelial cells exposed to the serum from the incompetent lower leg veins of the untreated CVD patients demonstrated higher stimulated synthesis of MMP-9 (+17%, P < .01), as well as increased markers of senescence (prolongation of population doubling time, ß-galactosidase activity, and expression of p21 and p53 genes). CVD serum-induced senescent endothelial cells had a higher expression of genes regulating IL-6, MMP-9, VCAM-1, and vWF synthesis. The overall proinflammatory effect on endothelial cells by the serum collected from the incompetent GSVs was stronger as compared with the serum from the systemic circulation. Serum collected from the veins after sulodexide treatment caused lower levels of endothelial cell inflammatory markers as well as respective gene expression than serum obtained at the beginning of the study (before sulodexide treatment). Sulodexide application also reduced the inflammatory secretory activity of the senescent endothelial cells. Sulodexide treatment resulted in the decrease of the majority of the studied inflammatory parameters in both lower limb incompetent vein and systemic blood. CONCLUSIONS: In patients with CVD, there are significant differences between circulating inflammatory markers analyzed from the lower leg incompetent GSV segments compared with the systemic circulation, indicating a higher inflammatory condition in CVD. Treatment with sulodexide reduces the proinflammatory and endothelial cell activation properties of the serum from patients with CVD. CLINICAL RELEVANCE: The study documented the significant proinflammatory human vascular endothelial cell activation when exposed to the serum collected from the varicose veins as compared with the serum from the systemic circulation in patients with chronic venous disease (CVD). The inflammatory marker expression, endothelial dysfunction, and endothelial cell senescence transformation can be successfully controlled and downregulated by patients' exposure to the glycosaminoglycan (sulodexide) treatment. Further studies are needed to confirm if glycosaminoglycan application can prevent further CVD clinical progression due to potential CVD-related pathological processes' modulation and their downregulation.

Recurrences and bleeding during extended treatment of patients with venous thromboembolism: results of the international, prospective, observational WHITE study.

BACKGROUND: Little data are available on real-life long-term treatments after a venous thromboembolism (VTE), and on recurrent VTE or bleeds events during treatments. METHODS: We investigated the complications occurring during follow-up (FU) in VTE patients who had received the treatment decisions given by the clinical centers, active in 7 countries (China, Czechia, Poland, Portugal, Russia, Slovakia, Tunisia), which participated in the international, prospective, observational WHITE study. RESULTS: FU information was collected in 1004 patients, recruited by 62 clinical centers (17 centers did not participate in FU collection). Extended treatments were proposed to 811 patients: direct oral anticoagulants (DOACs) (475), sulodexide (202), antiplatelet agents (73), vitamin K antagonists (VKAs) (45), low molecular weight heparin (LMWH) (16). All specific treatments were stopped in the remaining 193 patients. Patients who during FU used treatments different than those prescribed by the local investigators (263) or for other causes (26) were excluded from analysis. 50 primary events occurred throughout 1044 years FU in 715 patients, 4.8 incidence (×100 patient-years) [3.8 for recurrences, and 0.96 for bleeding (major or clinically relevant)]. Primary event incidence differed according to treatments (LMWH=33.3, antiplatelets =7.6, VKAs = 6.1, DOACs = 4.7, sulodexide = 4.2, all treatment stopped = 2.5), and differed across the involved countries. CONCLUSIONS: DOACs were the most used drugs for extended treatments. Overall, the rate of primary events during FU was low. The investigators identified patients at low risk of recurrence and high bleeding risk. Sulodexide use for secondary prevention deserves further studies.

Influence of clinical presentation, site, and extent of venous thrombosis on decision about duration of anticoagulation: Data from the international, prospective, observational WHITE study.

BACKGROUND: Low attention has generally been dedicated to the influence of clinical presentation, extent of venous thrombosis and presence of residual vein obstruction (RVO) on the decision about the duration of secondary prophylaxis after a first venous thromboembolism (VTE). AIM: This study aimed at investigating the role of the mentioned VTE characteristics on the therapeutic decision using the information collected in the international, prospective, observational WHITE study. RESULTS: 1240 patients were recruited by 79 clinical centers in 7 countries (China, Czechia, Poland, Portugal, Russia, Slovakia, and Tunisia). 35 patients had as index event a pulmonary embolism (PE) without a deep vein thrombosis (DVT), and all continued anticoagulation. We focused on the 1205 subjects with DVT. The treatment decision differed among countries; altogether, more than 85% of patients with proximal (with or without distal) DVT continued a prophylactic treatment with anticoagulants, or antithrombotics; 34% of patients with isolated distal DVT stopped treatment, and more than 85% of patients with a PE associated to a DVT continued treatment. At multivariable analysis, the presence of proximal DVT, signs of post-thrombotic syndrome (PTS), residual vein obstruction (RVO), maintenance <180 days and concomitant diseases was associated with increased probability to continue secondary prophylaxis. CONCLUSION: The presentation as proximal DVT (with or without PE) or isolated PE influenced the treating physicians' decision in favor of extension of secondary prophylaxis, together with the presence of concomitant diseases and local conditions which may increase the risk of post-thrombotic syndrome.

Unprovoked or provoked venous thromboembolism: not the prevalent criterion to decide on anticoagulation extension in clinical practice of various countries-the prospective, international, observational WHITE study.

The decision on treatment after a first venous thromboembolism (VTE) to prevent recurrences may be influenced by many factors. The prospective, observational, WHITE study aimed to analyze how this issue was tackled in every-day clinical practice in various countries, which have sensibly different socio-economic conditions and healthcare systems. Doctors active in 79 Internal or Vascular clinical centers in 7 countries (China, Czechia, Poland, Portugal, Russia, Slovakia, and Tunisia) enrolled VTE patients after the maintenance treatment phase. The present report analyzed information, collected in the central database, regarding the baseline characteristics, index events, type and duration of anticoagulant therapy and decision on post-maintenance treatment. From April 2018 to December 2020, 1240 patients were enrolled, 58% with an unprovoked index event. Direct oral anticoagulants (DOACs) were used in > 85% of all cases in China, Poland, Portugal, Russia and Czechia, in 52% in Slovakia and in no patient in Tunisia. The maintenance anticoagulation lasted in average approximately 6 months. Altogether, anticoagulation was stopped in 20%, extended in about 50%, regardless of whether the event was unprovoked or provoked and shifted to antithrombotics (mainly sulodexide or aspirin) in the remaining patients. In conclusion, some differences in VTE patient management were found between countries. The provoked/unprovoked nature of the index event, instead, was not the prevalent criterion to drive the decision on extension of anticoagulation, without large variations between countries. DOACs were the most widely used anticoagulant drugs, whereas > 25% of patients received antithrombotic drugs instead of anticoagulants as extended treatment.

An endovascular treatment of Chronic Cerebro-Spinal Venous Insufficiency in multiple sclerosis patients - 6 month follow-up results.

OBJECTIVE: In this study, the mid-term results (6 month follow-up) of the endovascular treatment in patients with Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and multiple sclerosis (MS) were prospectively evaluated. METHODS: Thirty-six patients with confirmed MS and CCSVI underwent endovascular treatment by the means of the uni- or bilateral jugular vein angioplasty with optional stent placement. All the patients completed 6 month follow-up. Their MS-related disability status and quality of life were evaluated 1, 3 and 6 months postoperatively by means of the following scales: Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale (MSIS-29), Epworth Sleepiness Scale (ESS), Heat Intolerance scale (HIS) and Fatigue Severity Scale (FSS). For patency and restenosis rate assessment, the control US duplex Doppler examination was used. RESULTS: Six months after the procedure, restenosis in post-PTA jugular veins was found in 33% of cases. Among 17 patients who underwent stent implantation into the jugular vein, restenosis or partial in-stent thrombosis was identified in 55% of the cases. At the 6 month follow-up appointment, there was no significant improvement in the EDSS or the ESS. The endovascular treatment of the CCSVI improved the quality of life according to the MSIS-29 scale but only up to 3 months after the procedure (with no differences in the 6 month follow-up assessment). Six months after the jugular vein angioplasty (with or without stent placement), a statistically significant improvement was observed only in the FSS and the HIS. CONCLUSIONS: The endovascular treatment in patients with MS and concomitant CCSVI did not have an influence on the patient's neurological condition; however, in the mid-term follow-up, an improvement in some quality-of-life parameters was observed.

Factors associated with the symptomatic status of carotid artery stenosis: identification in a cross-sectional study and development of a scoring system.

INTRODUCTION: The identification of asymptomatic patients at high risk of internal carotid artery (ICA) stenosis destabilization and symptom occurrence is crucial for prognosis estimation. OBJECTIVES: This study aimed to determine differences between patients with symptomatic and asymptomatic ICA stenosis and to develop a predictive model for the risk of symptomatic stenosis based on data collected in routine clinical practice. PATIENTS AND METHODS: The study included 163 patients with asymptomatic and 182 patients with symptomatic ICA stenosis greater than 70%. The study groups were compared in terms of stroke risk factors and comorbidities, coexisting ICA stenosis on the contralateral side, atherosclerosis in other arterial territories, and the morphology of atherosclerotic plaque assessed by transcervical ultrasound. RESULTS: Independent risk factors for symptomatic ICA stenosis included: male sex (odds ratio [OR], 2.94; 95% CI, 1.87-4.32; P <0.001), diabetes (OR, 2.86; 95% CI, 1.62-5.12; P <0.001), body mass index >25 kg/m2 (OR, 1.81; 95% CI, 1.72-1.86; P <0.001), chronic kidney disease (OR, 3.34; 95% CI, 1.34-8.87; P = 0.007), increased­risk features of ultrasound plaque morphology (OR, 2.52; 95% CI, 1.29-3.72; P = 0.009), and coexisting atherosclerosis in 3 or 4 vascular areas (OR, 3.72; 95% CI, 1.77-7.23; P <0.001).The sensitivity and specificity of the scoring model designed to estimate the risk of symptomatic ICA stenosis reached 77.6% and 76.9%, respectively. CONCLUSIONS: This cross­sectional study indicated that the analysis of selected imaging and clinical parameters may enable clinicians to estimate the risk of symptomatic ICA stenosis. The proposed scoring system requires further prospective validation.

Anticoagulation Duration After First Venous Thromboembolism: Real-Life Data From the International, Observational WHITE Study.

BACKGROUND: International guidelines recommend at least three months anticoagulation in all patients after acute venous thromboembolism (VTE) and suggest those with unprovoked events be considered for indefinite anticoagulation if the risk of recurrence is high and the risk of bleeding during treatment non-high. Other authors have recently argued against using a dichotomy unprovoked/provoked events to decide on anticoagulation duration and suggest instead using overall risk factors present in each patient as the basis for deciding. AIM: This sub-analysis of the WHITE study aimed at assessing the reasons for the treatment decisions taken by doctors in different countries. RESULTS: 1240 patients were recruited in 7 countries (China, Czechia, Poland, Portugal, Russia, Slovakia, and Tunisia). Anticoagulation was extended in 51.7% and 49.3% of patients with unprovoked or provoked events (n.s.); stopped in 15.4% versus 28.9% (P < .0001), and changed to antithrombotic drugs (sulodexide or aspirin) in 32.9% versus 21.8% (P < .0001). In the 430 subjects with isolated distal deep vein thrombosis (IDDVT) anticoagulation was stopped in 34.4%, continued in 37.0% (mainly those with post-thrombotic syndrome [PTS]) and switched to antithrombotics in the balance. High risk of recurrence was the most prevalent reason (>83% of cases) given to continue anticoagulation, regardless of nature and site of the index events, followed by risk of bleeding and presence of PTS signs. CONCLUSION: On average, attending physicians estimated the risk of recurrence in real life conditions, and the consequent therapeutic decision, using all the information available, not limiting to the location or nature of the index event.

Compression therapy for leg oedema in patients with heart failure.

The presence of chronic heart failure (CHF) results in a significant risk of leg oedema. Medical compression (MC) treatment is one of the basic methods of leg oedema elimination in patients with chronic venous disease and lymphedema, but it is not routinely considered in subjects with CHF-related swelling. In the study, an overview of the current knowledge related to the benefits and risk of using MC in the supportive treatment of leg oedema in CHF patients is presented. The available studies dedicated the comprehensive management of leg swelling using MC in CHF patients published in the English language literature till December 2019 were evaluated in term of the treatment efficacy and safety. In studies performed on CHF populations, manual lymphatic drainage, MC stocking, multilayer bandaged, as well as intermittent pneumatic compression or electric calf stimulations were used. The current evidence is based on non-randomized studies, small study cohorts, as well as very heterogenous populations. The use of the intermittent pneumatic compression in CHF patients significantly increases the right auricular pressure and mean pulmonary artery pressures as well as decreases systemic vascular resistance in most patients without the clinical worsening. The transient and rapid increase in the human atrial natriuretic peptide, after an application of the MC stocking in New York Heart Association (NYHA) class II patients was observed without clinical exacerbation. An application of the multilayer bandages in NYHA classes III and IV patients lead a significant increase in the right arterial pressure and lead to transient deterioration of the right and the left ventricular functions. In the manual lymphatic drainage study, aside from expected leg circumference reduction, no clinical worsening was observed. In a pilot study performed in a small cohort of CHF patients, electrical calf stimulation use resulted in a reduction in the lean mass of the legs without cardiac function worsening. The use of local leg compression can be considered stable CHF patients without decompensated heart function for both CHF-related oedema treatment and for treatment of the concomitant diseases leading to leg swelling occurrence. The use of MC in more severe classes of CHF (NYHA III and IV) should be the subject of future clinical studies to select the safest and most efficient compression method as well as to select the patients who benefit most from this kind of treatment.

Sulodexide increases mRNA expression of glutathione-related genes in human umbilical endothelial cells exposed to oxygen-glucose deprivation.

INTRODUCTION: Sulodexide (SDX), a heparinoid used to treat vascular diseases, exerts anti-ischemic properties. However, the underlying molecular mechanisms remain unclear. Induction of glutathione (GSH)-dependent genes protects against ischemia. Here, we investigated the effect of SDX on GSH-associated gene expression in human umbilical endothelial cells (HUVECs) using an in vitro ischemia model. METHODS: The transcriptional expression of GSH-related genes (GCLc, xCT, GS, GPx1 and GR) in HUVECs treated without/with SDX (0.5 LRU/ml) under oxygen-glucose deprivation (OGD) condition for 1-6 h was analyzed by real-time polymerase chain reaction. RESULTS: GCLc and xCT were strongly up-regulated by SDX in HUVECs in the first 2 h of OGD. GS and GPx1 mRNA expression levels were significantly increased during any time interval in ischemic HUVECs treated with SDX. Furthermore, incubation of HUVECs with SDX in OGD for 1-4 h resulted in enhanced expression of GR. CONCLUSIONS: Our studies provide the first evidence that SDX activates GSH-related genes in OGD-injured HUVECs.