Sushkov S.A.1, Nebylitsin Y.S.2, Pasevich D.M.1, Demidov S.I.1
The correction of endothelium functional state disturbances in patients with post-thrombotic syndrome of the lower extremities
1Vitebsk State Order of Peoples’ Friendship Medical University, Vitebsk, Republic of Belarus
2Vitebsk State Medical University Clinic, Vitebsk, Republic of Belarus
Vestnik VGMU. 2017;16(6):61-71.
Objectives. To optimize the approaches to the treatment of patients with post-thrombotic syndrome of the lower extremities veins by affecting the functional state of the blood vessels endothelium.
Material and methods. 35 patients (males – 24, females – 11) with post-thrombotic syndrome (PTS) were included in the study of the efficacy and results of treatment of the developed method. Depending on the provided treatment, patients were divided into two groups. In the first group, standard treatment regimen was used: anti-inflammatory drugs, antiaggregants, elastic compression. In the second group, the following drugs were included in the complex treatment regimen: phlebotropic drug – micronized purified flavonoid fraction – 500 mg (including diosmin (90%) – 450 mg and flavonoids in terms of hesperidin (10%) – 50 mg) (in form of the drug «Detraven») – 1000 mg per day during 30 days, angioprotector – pentoxifylline 0,08% – 250 ml during 10 days intravenously.
Results. It has been established that the use in the complex treatment of drugs: pentoxifylline, phlebotropic drug – micronized purified flavonoid fraction – 500 mg (including diosmin (90%) – 450 mg and flavonoids in terms of hesperidin (10%) – 50 mg) – 1000 mg a day for the purpose of correcting the functional state of the endothelium is pathogenetically grounded. An increase in endothelin-1 plasma concentration, an increase in interleukin-4 level, a decrease in the number of circulating endothelial cells, nitrates and nitrites content in the blood plasma, and the interleukin-6 level were observed. Regression of clinical manifestations of the disease was also noticed.
Conclusions. The conducted study confirmed the effectiveness of the use of drugs restoring the functional state of the endothelium in the complex treatment of patients with post-thrombotic syndrome of the veins of the lower extremities.
Key words: post-thrombotic syndrome, endothelial dysfunction, S-Nitrosylation.
1. Khryshchanovich VYa. Posttrombotichesky illness: diagnostics, treatment, prevention. Novosti Khirurgii. 2013;21(3):120-8. (In Russ.)
2. Burleva EL, Fokin AA, Ermolaev VL, Ivanov EV. Introduction to an angiologia and vascular surgery [Elektronnyi resurs]: ucheb posobie dlia studentov vuzov, internov i ordinatorov. Ekaterinburg, RF: Basko; 2015. 1 el opt disk. (In Russ.)
3. Kahn SR, Galanaud JP, Vedantham S, Ginsberg JS. Guidance for the prevention and treatment of the post-thrombotic syndrome. J Thromb Thrombolysis. 2016 Jan;41(1):144-53. doi: http://dx.doi.org/10.1007/s11239-015-1312-5
4. Katorkin SE, Kravtsov PF, Zhukov AA, Kushnarchuk MYu, Repin AA. Efficiency of use of a layer-by-layer dermatolipektomiya (Shave-Therapy) in complex treatment of patients with venous trophic ulcers of the lower extremities. Novosti Khirurgii. 2016;24(3):255-64. (In Russ.)
5. Rabinovich A, Cohen JM, Kahn SR. The predictive value of markers of fibrinolysis and endothelial dysfunction in the post thrombotic syndrome. A systematic review. Thromb Haemost. 2014 Jun;111(6):1031-40. doi: http://dx.doi.org/10.1160/TH13-11-0931
6. Komarów W, Hawro P, Lekston A, Urbanek T, Zagrodzki P. Endothelial dysfunction in patients with chronic venous disease: an evaluation based on the flow-mediated dilatation test. Int Angiol. 2015 Feb;34(1):36-42.
7. Shamaraeva IV, Ponomareva IP, Proshchaev KI. Varicose veins of the lower extremities in the elderly: peculiarities and possibilities of medical correction. Fundam Issled. 2014;(7-4):807-11. (In Russ.)
8. Spath P, Tisato V, Gianesini S, Tessari M, Menegatti E, Manfredini R, et al. The calendar of cytokines: Seasonal variation of circulating cytokines in chronic venous insufficiency. JRSM Cardiovasc Dis.2017 Sep;6:2048004017729279. doi: http://dx.doi.org/10.1177/2048004017729279
9. Raffetto JD, Mannello F. Pathophysiology of chronic venous disease. Int Angiol. 2014 Jun;33(3):212-21.
10. Nebylitsin YuS, Sushkov SA, Solodkov AP, Doroshenko AS. Endothelial dysfunction in acute and chronic venous insufficiency. Novosti Khirurgii. 2008;16(4):141-53. (In Russ.)
11. Dubinina EE. The role of reactive oxygen species as signaling molecules in tissue metabolism under oxidative stress condition. Vopr Med Khimii. 2001;47(6):561-81. (In Russ.)
12. Kiseleva NI. Comparative characteristics of hypotensive and antioxidant drugs in the treatment of preeclampsia. Vestn VGMU. 2007;6(2):77-84. (In Russ.)
13. Piskun DV, Semenov VM, Solodkov AP, Kutuzova AV. The use of pentoxifylline for the treatment of patients with bacterial intestinal infections complicated by the development of vascular disease. Immunopatologiia Allergologiia Infektologiia. 2007;(1):61-5. (In Russ.)
14. Hladovec J. Circulating endothelial cells as a sign of vessels wall lesions. Physiol Bohemoslov. 1978;27(2):140-4.
15. Veremey IS, Solodkov AP, Osochuk SS. A modified method for the determination of NO3 and NO2 with zinc dust in the presence of ammonia complex of copper sulfate. V: Disfunktsiia endoteliia: eksperimental'nye i klinicheskie issledovaniia: sb tr resp nauch-prakt konf. Vitebsk, RB; 2000. Р. 112-5. (In Russ.)
16. Pocock ES, Alsaigh T, Mazor R, Schmid-Schönbein GW. Cellular and molecular basis of Venous insufficiency. Vasc Cell. –2014;(6):24. doi.org/10.1186/s13221-014-0024-5
17. 7. Schmid-Shenbein GW, Takase S, Bergan JJ. New advances in the understanding of the pathophysiology of chronic venous insufficiency. Angiology. 2001 Aug;52 Suppl 1:S27-34.
18. Agren MS, Eaglestein WH, Feguson MW, Harding KG, Moore K, Saarialho-Kere UK, et al. Causes and effects of the chronic inflammation in venous leg ulcers. Acta Derm Venereol Suppl (Stockh). 2000;210:3-17.
19. Bergan J. Molecular mechanisms in chronic venous insufficiency. Ann Vasc Surg. 2007 May;21(3):260-6. doi: http://dx.doi.org/10.1016/j.avsg.2007.03.011
20. Harasstani OA, Moin S, Tham CL, Liew CY, Ismail N, Rajajendram R, et al. Flavonoid combinations cause synergistic inhibition of proinflammatory mediator secretion from lipopolysaccharide-induced RAW 264.7 cells. Inflamm Res. 2010 Sep;59(9):711-21. doi: http://dx.doi.org/10.1007/s00011-010-0182-8
21. Bergan JJ. Chronic venous insufficiency and the therapeutic effects of Daflon 500 mg. Angiology. 2005 Sep-Oct;56 Suppl 1:S21-4. doi: http://dx.doi.org/10.1177/00033197050560i104
22. Antignani PL. Medical Treatment of Chronic Venous Disease. SM J Pharmac Ther. 2017;3(1):1015.
23. Park HH, Lee S, Son HY, Park SB, Kim MS, Choi EJ, et al. Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells. Arch Pharm Res. 2008 Oct;31(10):1303-11. doi: http://dx.doi.org/10.1007/s12272-001-2110-5
Information about authors:
Sushkov S.A. – Candidate of Medical Sciences, associate professor, pro-rector for scientific research work, Vitebsk State Order of Peoples’ Friendship Medical University;
Nebylitsin Y.S. – Candidate of Medical Sciences, associate professor, head of the Department of Plastic Surgery & Cosmetology, Vitebsk State Medical University Clinic;
Pasevich D.M. – lecturer of the Chair of General Surgery, Vitebsk State Order of Peoples’ Friendship Medical University;
Demidov S.I. – lecturer of the Chair of General Surgery, Vitebsk State Order of Peoples’ Friendship Medical University.