BackgroundThe ischemia-reperfusion injury (IRI) is unavoidable in vascular surgery. Damage to the microcirculation and endothelial glycocalyx might set up a shock with loss of circulatory coherence and organ failure. Sulodexide may help to protect endothelial glycocalyx and alleviate the ischemia-reperfusion injury.MethodsTwenty female piglets underwent surgery with a 30-min-long suprarenal aortic clamp, followed by two hours of reperfusion. Ten piglets received sulodexide before the clamp, and 10 received normal saline. Blood and urine samples were taken at baseline and in 20-min intervals until the 120th minute to analyze the serum syndecan-1, E-selectin, and thrombomodulin. Albumin and glycosaminoglycans were examined in the urine. The kidney biopsies before and after the protocol were examined by light microscopy with hematoxylin-eosin staining. The sublingual microcirculation was recorded by side-stream dark field imaging at the time as blood and urine.ResultsBased on the 2-way ANOVA testing, there was no statistically significant difference in the parameters of sublingual microcirculation. Serum markers of endothelial cell activation and damage (E-selectin and thrombomodulin) did not show any statistically significant difference either. Syndecan-1, a marker of glycocalyx damage, showed statistically significantly higher values based on the 2-way ANOVA testing (p < 0.0001) with the highest difference in the 80th minute: 7.8 (3.9-44) ng/mL in the control group and 1.8 (0.67-2.8) ng/mL in the sulodexide group. In the urine, the albuminuria was higher in the control group, although not statistically significant. Glycosaminoglycans were statistically significantly higher in the sulodexide group based on the mixed-effect analysis due to the intervention itself. Histological analysis of the renal biopsies showed necrosis in both groups after reperfusion.ConclusionAdministering sulodexide significantly reduced the level of endothelial markers of IRI. The study results support further research into using preemptive administration of sulodexide to modulate IRI in clinical medicine.
- MeSH
- E-Selectin blood MeSH
- Glycocalyx MeSH
- Glycosaminoglycans * pharmacology therapeutic use MeSH
- Kidney pathology blood supply MeSH
- Microcirculation drug effects MeSH
- Disease Models, Animal MeSH
- Swine MeSH
- Reperfusion Injury * prevention & control MeSH
- Syndecan-1 blood MeSH
- Thrombomodulin blood MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BackgroundSulodexide is a glycosaminoglycan-based drug prescribed to patients with angiopathy. We performed a pilot study to investigate whether sulodexide positively modulates the endothelial glycocalyx (EG) layer and the microcirculation in a porcine model of EG enzymatic damage. The EG is a sugar-based endothelial lining that is involved in the physiology of the capillary wall and the pathogenesis of many diseases.MethodsEG damage was induced in eight piglets by hyaluronidase III and heparanase I given intravenously. Four animals received sulodexide 600 IU intravenously before the enzymes and four animals after the enzymes were administered. Four animals constituted a control group. Sublingual microcirculation by side-stream dark field imaging and plasmatic concentration of syndecan-1 by ELISA were measured at baseline, 20 min after intervention, and at the 40th, and 60th minute onwards. The statistics were performed with a one-way ANOVA test with Turkey's correction for multiple comparisons testing. Timepoint comparison was performed by Student t-test or Mann-Whitney test.ResultsAt baseline, there were no statistically significant differences between the animal groups. After the intervention, the levels of syndecan-1 were significantly lower in the control group. While there were no differences between the two intervention groups. The sublingual microcirculation analysis showed that the DeBacker score was significantly higher in the control group. At 60 min, there was also a statistically significant difference in DeBacker score between the groups (8.1 ± 1.6 mm-1 in the group with enzymes given first and 11 ± 0.92 mm-1 in the group with sulodexide given first, p = 0.03). The analysis of the proportion of perused vessels did not show any statistically significant differences.ConclusionThe results of the study demonstrated a working model of EG damage but no specific action of sulodexide on EG modulation. In the sublingual microcirculation analysis, the sulodexide reduced the fall in absolute tissue perfusion in 60 min.
- MeSH
- Endothelium, Vascular * drug effects MeSH
- Glycocalyx * drug effects metabolism MeSH
- Glycosaminoglycans * pharmacology MeSH
- Hyaluronoglucosaminidase MeSH
- Microcirculation drug effects MeSH
- Disease Models, Animal MeSH
- Pilot Projects MeSH
- Swine MeSH
- Syndecan-1 blood MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Keywords
- sulodexid, apixaban,
- MeSH
- Anticoagulants * pharmacology therapeutic use MeSH
- Varicose Ulcer * drug therapy nursing MeSH
- Pulmonary Disease, Chronic Obstructive MeSH
- Diosmin pharmacology therapeutic use MeSH
- Erysipelas drug therapy MeSH
- Glycosaminoglycans pharmacology therapeutic use MeSH
- Wound Healing MeSH
- Hyperbaric Oxygenation methods MeSH
- Respiratory Tract Infections etiology drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Penicillin G pharmacology therapeutic use MeSH
- Pyrazoles pharmacology therapeutic use MeSH
- Pyridones pharmacology therapeutic use MeSH
- Rivaroxaban pharmacology therapeutic use MeSH
- Aged MeSH
- Warfarin adverse effects MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Chronické rány jsou u systémových onemocnění obvykle špatně léčitelné a vyžadují multioborovou spolupráci. Terapie vychází z léčby primárního onemocnění. V první kazuistice se budu věnovat systémovému lupus erythematodes (SLE) se sekundárním antifosfolipidovým syndromem u pacientky s chronickým vředem na bérci. Antifosfolipidový syndrom je spojený s vyšším rizikem trombóz a potratu. Druhá kazuistika je o mladé ženě s mnohočetnými ulceracemi na nohách, po jejichž příčině jsem pátrala. Zjištěna byla pouze pozitivita protilátek anti-DFS70 při negativitě ENA protilátek. U obou pacientek došlo po nasazení sulodexidu k velmi rychlému hojení vředů na kůži.
Chronic wounds are usually difficult to treat in systemic diseases and require multidisci- plinary collaboration. Wound management is based on the treatment of the primary disease. In the first case report I will discuss systemic lupus erythematosus with secondary antiphospholipid syndrome in a patient with chronic shin ulcer. Antiphospholipid syndrome is associated with a higher risk of trombosis and abortion. The second case report is about a young woman with multiple ulcers on her legs, and I was looking for the reason. Only anti DFS70 antibody positivity was found, with ENA antibody negativity. In both patients, the healing of the ulcer on the skin was very fast after the initiation of sulodexide treatment.
- Keywords
- sulodexid, anti-DFS70,
- MeSH
- Antiphospholipid Syndrome MeSH
- Autoantibodies MeSH
- Glycosaminoglycans * administration & dosage therapeutic use MeSH
- Wound Healing * drug effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Pyoderma Gangrenosum * etiology drug therapy therapy MeSH
- Lupus Erythematosus, Systemic complications MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Ve dvou kazuistikách uvádím efekt perorálních antikoagulancií na dlouhodobě se nehojící žilní ulcerace. V první kazuistice se jedná o pacientku s těžkou chronickou obstrukční plicní chorobou, s ulceracemi na obou bércích, trvajícími léta. Ve druhé kazuistice je popsán pacient po erysipelu s mnohočetnými vředy na bércích. V obou případech jsem indikovala převod pacientů z antagonisty vitamínu K na přímá antikoagulancia NOAC, oba pacienti současně užívali sulodexid. Jaké výsledky přinesla sonikace v léčbě chronických ulcerací se dočtete v následujících kazuistikách.
In two case reports, I present the effect of oral anticoagulants on long-term non-healing venous ulcers. In the first case report, a patient with severe chronic obstructive pulmonary disease, with ulcera- tions on both lower legs, lasting for years. In the second case report, a patient with multiple ulcers on the lower legs after erysipelas. In both cases, I indicated the transfer of patients from a vitamin K antagonist to NOAC – novel oral anticoagulants, both patients were taking suledoxide at the same time. In the third case report, a patient in a wheelchair, with ulcerations on both lower legs, lasting for years. What results sonication brought in the treatment of chronic ulcerations can be found in the following case reports.
- MeSH
- Anticoagulants adverse effects MeSH
- Varicose Ulcer * complications therapy MeSH
- Biological Dressings MeSH
- Glycosaminoglycans therapeutic use MeSH
- Wound Healing * drug effects MeSH
- Wound Infection therapy MeSH
- Comorbidity MeSH
- Middle Aged MeSH
- Humans MeSH
- Drug Substitution MeSH
- Aged MeSH
- Sonication methods MeSH
- Warfarin adverse effects MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Úvod: Chirurgická léčba je spojena s nežádoucí reakcí organismu na tzv. chirurgické trauma, která je označována jako chirurgický stres. Jednou z jeho základních příčin je ischemicko-reperfuzní poškození tkání, které zahrnuje funkční a strukturální změny v tkáních. Ty vznikají po obnovení průtoku krve po epizodě ischemie. Dochází k nekróze ireverzibilně změněných buněk či otoku tkání vznikajícímu na podkladě endoteliální a mitochondriální dysfunkce. Metody: Fyziologie, patofyziologie endoteliálního glykokalyxu: Endoteliální glykokalyx je 0,2 až 5 mikrometrů vysoká heteropolysacharidová vrstva pokrývající endotel na jeho intraluminální straně. Páteřními molekulami glykokalyxu jsou proteoglykany, na které se vážou glykoproteiny a glykosaminoglykany. Poškození endoteliálního glykokalyxu bylo dokumentováno u traumatu, u pacientů se septickým šokem, při ischemicko-reperfuzním poškození či při rozsáhlých chirurgických výkonech. Postupy prevence poškození endoteliálního glykokalyxu: Jako prevence ischemicko-reperfuzního poškození tkání byla zkoumána metoda vzdálené prekondice ischemie. Provedené metaanalýzy přínos tohoto postupu v chirurgii ale nepotvrdily. Farmakologicky může být bráněno poškození glykokalyxu látkami, jako jsou antitrombin III, doxycyklin, hydrokortizon, etanercept či dárci oxidu dusnatého. Protektivně na glykokalyx působí také albumin a inhalace vodíku. Protektivní a reparační účinek na glykokalyx vykazuje také sulodexid. Jedná se o proteoglykan působící antitromboticky, fibrinolyticky, hypofibrinogenemicky a lipolyticky. Současná indikace sulodexidu je v léčbě žilních onemocnění, ischemické choroby srdeční a ischemické choroby dolních končetin. Byl prokázán pozitivní efekt sulodexidu na renální poškození při modelování ischemie a reperfuze a na reparaci endotelu po jeho mechanickém poškození. Závěr: Prostor pro další zkoumání se otevírá směrem k prokázání účinku endotelprotektiv prostřednictvím reparace endoteliálního glykokalyxu při ischemicko-reperfuzním poškození na modelu velkého laboratorního zvířete a také při klinické studii u pacientů podstupujících cévně rekonstrukční výkon.
Introduction: Surgical treatment is associated with an unwanted response of the organism to the so-called surgical trauma. This response is called surgical stress. Ischaemia-reperfusion injury is one of essential causes of tissue damage. It comprises functional and structural changes in tissue that occur after the restoration of circulation, after an episode of ischaemia. Necrosis of irreversibly changed cells and endothelial and mitochondrial-induced tissue swelling occur. Methods: Physiology, pathophysiology of endothelial glycocalyx: Endothelial glycocalyx is a 0.2 to 5 micrometres thin heteropolysaccharide layer that covers the endothelium on its intraluminal side. Backbone molecules of the glycocalyx include proteoglycans, glycoproteins, and glycosaminoglycans. Damage of the endothelial glycocalyx was described in trauma patients, in patients with septic shock, in ischemia and reperfusion injury, and during extensive surgical procedures. Approaches to prevent endothelial glycocalyx damage: Remote ischemic preconditioning was tested as a method of ischemia and reperfusion injury prevention during and after surgery. Nevertheless, the expected effect was not confirmed in performed meta-analyses. Endothelial glycocalyx damage can be prevented pharmacologically with a broad spectrum of substances, such as antithrombin III, doxycycline, hydrocortisone, etanercept, or nitric oxide donors. Hydrogen inhalation or albumin affects glycocalyx positively. Sulodexide provides a positive effect on the protection and reparation of endothelial glycocalyx. This proteoglycan with antithrombotic, fibrinolytic, hypofibrinogenemic, and lipolytic function is used for the treatment of venous diseases, ischaemic heart disease, and peripheral arterial disease. A positive effect of sulodexide on renal dysfunction was documented in a model of ischaemia and reperfusion injury. Equally, a positive effect of sulodexide was described on endothelium repair after its mechanical damage. Conclusion: Further research needs to be performed to evaluate the effect of endothelium-protectives on glycocalyx damage prevention and repair in ischaemia and reperfusion models involving large laboratory animals or in clinical trials in patients undergoing surgical revascularisation procedures.
- MeSH
- Surgical Procedures, Operative adverse effects MeSH
- Glycocalyx * physiology pathology MeSH
- Hematologic Agents pharmacology classification therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Postoperative Complications drug therapy prevention & control MeSH
- Reperfusion Injury etiology prevention & control MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
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.
- MeSH
- Anticoagulants therapeutic use MeSH
- Administration, Oral MeSH
- Fibrinolytic Agents MeSH
- Heparin, Low-Molecular-Weight adverse effects MeSH
- Hemorrhage chemically induced epidemiology MeSH
- Humans MeSH
- Prospective Studies MeSH
- Venous Thromboembolism * drug therapy epidemiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
