Preview

Стационарозамещающие технологии: Амбулаторная хирургия

Расширенный поиск

Патогенетическое обоснование флеботропной терапии хронических заболеваний вен

https://doi.org/10.21518/1995-1477-2019-3-4-19-33

Полный текст:

Аннотация

Хронические заболевания вен (ХЗВ) являются самой распространенной сосудистой патологией, оказывающей значительное негативное физическое и психологическое воздействие на пациентов, а также требующей больших экономических затрат со стороны национальных систем здравоохранения. В последние десятилетия был выявлен ряд факторов риска ХЗВ, но лишь недавно стала обсуждаться роль воспаления и дисфункции эндотелия. Современные знания позволяют выделить несколько приоритетных стратегий и целей, направленных на коррекцию основных патофизиологических механизмов развития и прогрессирования ХЗВ. В частности, применение веноактивных препаратов, роль которых в повышении тонуса и сократимости вен, уменьшении воспаления и отека, а также улучшении микроциркуляции и ускорении заживления венозных язв была тщательно изучена и с положительными результатами представлена в различных публикациях. В данном обзоре представлены различные патофизиологические механизмы развития ХЗВ, которые и служат целями для лекарственной терапии с помощью ряда веноактивных препаратов.

Об авторах

В. Ю. Богачев
Российский национальный исследовательский медицинский университет имени Н. И. Пирогова, Первый флебологический центр
Россия

д.м.н., профессор, кафедра факультетской хирургии № 2

117997, Россия, Москва, ул. Островитянова, д. 1

117447, Россия, Москва, ул. Дмитрия Ульянова, д. 31



А. Мансилья
Университет Порто
Португалия

доктор, профессор, директор отдела ангиологии и сосудистой хирургии медицинского факультета

Португалия, Порто, ул. Хулио Диниса, 826, 5



Б. В. Болдин
Российский национальный исследовательский медицинский университет имени Н. И. Пирогова
Россия

д.м.н., профессор, заведующий кафедрой факультетской хирургии № 2

 117997, Россия, Москва, ул. Островитянова, д. 1



С. В. Родионов
Российский национальный исследовательский медицинский университет имени Н. И. Пирогова
Россия

д.м.н., профессор, кафедра факультетской хирургии № 2

 117997, Россия, Москва, ул. Островитянова, д. 1



О. В. Дженина
Первый флебологический центр
Россия

к.м.н., врач-флеболог

117447, Россия, Москва, ул. Дмитрия Ульянова, д. 31



Список литературы

1. Bergan J.J., Schmid-Schonbein G.W., Smith P.D., Nicolaides A.N., Boisseau M.R., Eklof B. Chronic venous disease. N Engl J Med. 2006;(355):488–498. doi: 10.1056/NEJMra055289.

2. Eberhardt R.T., Raffetto J.D. Chronic venous insufficiency. Circulation. 2014;(130):333–346. doi: 10.1161/CIRCULA-TIONAHA.113.006898.

3. Eklof B., Rutherford R.B., Bergan J.J., Carpentier P.H., Gloviczki P., Kistner R.L., Meissner M.H., Moneta G.L., Myers K., Padberg F.T., Perrin M., Ruckley C.V., Smith P.C., Wakefield T.W. Revision of the CEAP classification for chronic venous disorders: Consensus statement. J Vasc Surg. 2004;(40):1248–1252. doi: 10.1016/j.jvs.2004.09.027.

4. Beebe-Dimmer J.L., Pfeifer J.R., Engle J.S., Schottenfeld D. The epidemiology of chronic venous insufficiency and varicose veins. Ann. Epidemiol. 2005;(15):175–184. doi: 10.1016/j.annepidem.2004.05.015.

5. Rabe E., Guex J.J., Puskas A., Scuderi A., Fernandez Quesada F. Epidemiology of chronic venous disorders in geographically diverse populations: Results from the Vein Consult Program. Int. Angiol. 2012;(31):105–115. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22466974.

6. Carpentier P.H., Maricq H.R., Biro C., Poncot-Makinen, C.O., Franco A. Prevalence, risk factors, and clinical patterns of chronic venous disorders of lower limbs: A population-based study in France. J Vasc Surg. 2004;(40):650–659. doi: 10.1016 / j.jvs.2004.07.025.

7. Wrona M., Jockel K.H., Pannier F., Bock E., Hoffmann B., Rabe E. Association of Venous Disorders with Leg Symptoms: Results from the Bonn Vein Study 1. Eur J Vasc Endovasc Surg. 2015;(50):360–367. doi: 10.1016 / j.ejvs.2015.05.013.

8. Evans C.J., Fowkes F.G., Ruckley C.V., Lee A.J. Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study. J Epidemiol Commun Health. 1999;(53):149–153. doi: 10.1136/jech.53.3.149.

9. Robertson L., Lee A.J., Evans C.J., Boghossian S., Allan P.L., Ruckley C.V., Fowkes F.G. Incidence of chronic venous disease in the Edinburgh Vein Study. J Vasc Surg Venous Lymphat Disord. 2013;(1):59–67. doi: 10.1016/j.jvsv.2012.05.006.

10. Fowkes F.G., Evans C.J., Lee A.J. Prevalence and risk factors of chronic venous insufficiency. Angiology. 2001;(52):5–15. doi: 10.1177/0003319701052001S02.

11. Jawien A. The influence of environmental factors in chronic venous insufficiency. Angiology. 2003;(54):19–31. doi: 10.1177/0003319703054001S04.

12. Ruckley C.V., Evans C.J., Allan P.L., Lee A.J., Fowkes F.G. Chronic venous insufficiency: Clinical and duplex correlations. The Edinburgh Vein Study of venous disorders in the general population. J Vasc Surg. 2002;(36):520–525. doi: 10.1067/mva.2002.126547.

13. Fowkes F.G., Lee A.J., Evans C.J., Allan P.L., Bradbury A.W., Ruckley C.V. Lifestyle risk factors for lower limb venous reflux in the general population: Edinburgh Vein Study. Int J Epidemiol. 2001;(30):846–852. doi: 10.1016/s0895–4356(02)00518–8.

14. Lacroix P., Aboyans V., Preux P.M., Houles M.B., Laskar M. Epidemiology of venous insufficiency in an occupational population. Int Angiol. 2003;(22):172–176. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12865883.

15. Robertson L., Evans C., Fowkes F.G. Epidemiology of chronic venous disease. Phlebology. 2008;(23):103–111. doi: 10.1258/phleb.2007.007061.

16. Brand F.N., Dannenberg A.L., Abbott R.D., Kannel W.B. The epidemiology of varicose veins: The Framingham Study. Am J Prevent Med. 1988;(4):96–101. Available at: https://www.ncbi.nlm.nih.gov/pubmed/3395496.

17. Pannier F., Rabe E. The relevance of the natural history of varicose veins and refunded care. Phlebology. 2012;(27):23–26. doi: 10.1258/phleb.2012.012S23.

18. Lee A.J., Robertson L.A., Boghossian S.M., Allan P.L., Ruckley C.V., Fowkes F.G., Evans C.J. Progression of varicose veins and chronic venous insufficiency in the general population in the Edinburgh Vein Study. J Vasc Surg Venous Lymphat Disord. 2015;(3):18–26. doi: 10.1016/j.jvsv.2014.09.008.

19. Kahn S.R., M’Lan C.E., Lamping D.L., Kurz X., Berard A., Abenhaim L.A. Relationship between clinical classification of chronic venous disease and patient-reported quality of life: Results from an international cohort study. J Vasc Surg. 2004;(39):823–828. doi: 10.1016/j.jvs.2003.12.007.

20. Van Korlaar I., Vossen C., Rosendaal F., Cameron L., Bovill E., Kaptein A. Quality of life in venous disease. Thromb Haemost. 2003;(90):27–35.

21. Lafuma A., Fagnani F., Peltier-Pujol F., Rauss A. [Venous disease in France: An unrecognized public health problem] [Article in French]. J Mal Vasc. 1994;(19):185–189. Available at: https://www.ncbi.nlm.nih.gov/pubmed/7798803.

22. McGuckin M., Waterman R., Brooks J., Cherry G., Porten L., Hurley S., Kerstein M.D. Validation of venous leg ulcer guidelines in the United States and United Kingdom. Am J Surg. 2002;(183):132–137. doi: 10.1016/s0002–9610(01)00856-x.

23. Launois R., Le Moine J.G., Lozano F.S., Mansilha A. Construction and international validation of CIVIQ-14 (a short form of CIVIQ-20), a new questionnaire with a stable factorial structure. Qual Life Res. 2012;(21):1051–1058. doi: 10.1007/s11136-011-0008–3.

24. Launois R., Mansilha A., Jantet G. International psychometric validation of the Chronic Venous Disease quality of life Questionnaire (CIVIQ-20). Eur J Vasc Endovasc Surg. 2010;(40):783–789. doi: 10.1016/j.ejvs.2010.03.034.

25. Launois R., Mansilha A., Lozano F. Linguistic validation of the 20 item-chronic venous disease quality-of-life questionnaire (CIVIQ-20). Phlebology. 2014;(29):484–487. doi: 10.1177/0268355513479582.

26. Launois R. Health-related quality-of-life scales specific for chronic venous disorders of the lower limbs. J Vasc Surg Venous Lymphat Disord. 2015;(3):219–227.e1–3. doi: 10.1016/j.jvsv.2014.08.005.

27. Da Silva A., Navarro M.F., Batalheiro J. The importance of chronic venous insufficiency. Various preliminary data on its medico-social consequences. Phlebologie. 1992;(45):439–443. Available at: https://www.ncbi.nlm.nih.gov/pubmed/1302319.

28. Laing W. Chronic Venous Diseases of the Leg. Office of Health Economics: London, UK; 1992. Available at: https://pdfs.semanticscholar.org/72ad/b07ccadb0b0026018bb8a37a0d98f56186d6.pdf.

29. Purwins S., Herberger K., Debus E.S., Rustenbach S.J., Pelzer P., Rabe E., Schafer E., Stadler R., Augustin M. Cost-of-illness of chronic leg ulcers in Germany. Int Wound J. 2010;(7):97–102. doi: 10.1111/j.1742-481X.2010.00660.x.

30. Rabe E., Pannier F. Societal costs of chronic venous disease in CEAP C4, C5, C6 disease. Phlebology. 2010;(25):64–67. doi: 10.1258/phleb.2010.010s09.

31. Padberg F. The physiology and hemodynamics of the normal venous circulation. In: Gloviczki P., Yao J. (eds.). Handbook of Venous Disorders. 2nd ed. Arnold Publisher: New York, NY, USA; 2001:25–35.

32. Bergan J. Molecular mechanisms in chronic venous insufficiency. Ann Vasc Surg. 2007;(21):260–266. doi: 10.1016/j.avsg.2007.03.011.

33. Pocock E.S., Alsaigh T., Mazor R., Schmid-Schonbein G.W. Cellular and molecular basis of Venous insufficiency. Vasc Cell. 2014;(6):24. doi: 10.1186/s13221-014-0024–5.

34. Castro-Ferreira R., Cardoso R., Leite-Moreira A., Mansilha A. The Role of Endothelial Dysfunction and Inflammation in Chronic Venous Disease. Ann Vasc Surg. 2018;(46):380–393. doi: 10.1016/j.avsg.2017.06.131.

35. Howlader M.H., Coleridge Smith P.D. Relationship of plasma vascular endothelial growth factor to CEAP clinical stage and symptoms in patients with chronic venous disease. Eur J Vasc Endovasc Surg. 2004;(27):89–93. doi: 10.1016/j.ejvs.2003.10.002.

36. Shoab S.S., Scurr J.H., Coleridge-Smith P.D. Increased plasma vascular endothelial growth factor among patients with chronic venous disease. J Vasc Surg. 1998;(28):535–540. Available at: https://core.ac.uk/download/pdf/82228001.pdf.

37. Tisato V., Zauli G., Gianesini S., Menegatti E., Brunelli L., Manfredini R., Zamboni P., Secchiero P. Modulation of circulating cytokinechemokine profile in patients affected by chronic venous insufficiency undergoing surgical hemodynamic correction. J Immunol Res. 2014;2014:473765. doi: 10.1155/2014/473765.

38. Kowalewski R., Malkowski A., Sobolewski K., Gacko M. Evaluation of aFGF / bFGF and FGF signaling pathway in the wall of varicose veins. J Surg Res. 2009;(155):165–172. doi: 10.1016/j.jss.2008.07.032.

39. Traub O., Berk B.C. Laminar shear stress: Mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler Thromb Vasc Biol. 1998;(18):677–685. doi: 10.1161/01.ATV.18.5.677.

40. Xiao Y., Huang Z., Yin H., Lin Y., Wang S. In vitro differences between smooth muscle cells derived from varicose veins and normal veins. J Vasc Surg. 2009;(50):1149–1154. Available at: https://core.ac.uk/download/pdf/82304258.pdf.

41. Badier-Commander C., Couvelard A., Henin D., Verbeuren T., Michel J.B., Jacob M.P. Smooth muscle cell modulation and cytokine overproduction in varicose veins. An in situ study. J Pathol. 2001;(193):398–407. doi: 10.1002/path.819.

42. Moazzam F., DeLano F.A., Zweifach B.W., Schmid-Schonbein G.W. The leukocyte response to fluid stress. Proc Natl Acad Sci USA. 1997;(94):5338–5343. doi: 10.1073/pnas.94.10.5338.

43. Fukuda S., Schmid-Schonbein G.W. Regulation of CD18 expression on neutrophils in response to fluid shear stress. Proc Natl Acad Sci USA. 2003;(100):13152–13157. doi: 10.1073/pnas.2336130100.

44. Berk B.C., Abe J.I., Min W., Surapisitchat J., Yan C. Endothelial atheroprotective and anti-inflammatory mechanisms. Ann N Y Acad Sci. 2001;(947):93–109; discussion 109–111. doi: 10.1111/j.1749–6632.2001.tb03932.x.

45. Sorescu G.P., Sykes M., Weiss D., Platt M.O., Saha A., Hwang J., Boyd N., Boo Y.C., Vega J.D., Taylor W.R. et al. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response. J Biol Chem. 2003;(278):31128–31135.

46. Tarbell J.M., Cancel L.M. The glycocalyx and its significance in human medicine. J Int Med. 2016;(280):97–113. doi: 10.1111/joim.12465.

47. Constantinescu A.A., Vink H., Spaan J.A. Endothelial cell glycocalyx modulates immobilization of leukocytes at the endothelial surface. Arterioscler Thromb Vasc Biol. 2003;(23):1541–1547. doi: 10.1161/01.ATV.0000085630.24353.3D.

48. Mulivor A.W., Lipowsky H.H. Role of glycocalyx in leukocyteendothelial cell adhesion. Am J Physiol Heart Circ Physiol. 2002;(283):H1282 – H1291. doi: 10.1152/ajpheart.00117.2002.

49. Poredos P., Spirkoska A., Rucigaj T., Fareed J., Jezovnik M.K. Do blood constituents in varicose veins differ from the systemic blood constituents? Eur J Vasc Endovasc Surg. 2015;(50):250–256. doi: 10.1016/j.ejvs.2015.04.031.

50. Sola Ldel R., Aceves M., Duenas A.I., Gonzalez-Fajardo J.A., Vaquero C., Crespo M.S., Garcia-Rodriguez C. Varicose veins show enhanced chemokine expression. Eur J Vasc Endovasc Surg. 2009;(38):635–641. doi: 10.1016/j.ejvs.2009.07.021.

51. Tisato V., Zauli G., Voltan R., Gianesini S., di Iasio M.G., Volpi I., Fiorentini G., Zamboni P., Secchiero P. Endothelial cells obtained from patients affected by chronic venous disease exhibit a pro-inflammatory phenotype. PLoS ONE. 2012;(7):e39543. doi: 10.1371/journal.pone.0039543.

52. Moyses C., Cederholm-Williams S.A., Michel C.C. Haemoconcentration and accumulation of white cells in the feet during venous stasis. Int J Microcirc Clin Exp. 1987;(5):311–320. Available at: https://www.ncbi.nlm.nih.gov/pubmed/3557818.

53. Thomas P.R., Dormandy J.A. White cell and platelet trapping in patients with chronic venous insufficiency. Phlebologie. 1988;(41):771–776. Available at: https://www.ncbi.nlm.nih.gov/pubmed/3247394.

54. Wilkinson L.S., Bunker C., Edwards J.C., Scurr J.H., Smith P.D. Leukocytes: Their role in the etiopathogenesis of skin damage in venous disease. J Vasc Surg. 1993;(17):669–675. Available at: https://www.ncbi.nlm.nih.gov/pubmed/8464084.б

55. Coleridge Smith P.D. The microcirculation in venous hypertension. Vasc Med. 1997;(2):203–213. Available at: https://journals.sagepub.com/doi/pdf/10.1177/1358863X9700200306.

56. Burnand K.G., Whimster I., Clemenson G., Thomas M.L., Browse N.L. The relationship between the number of capillaries in the skin of the venous ulcer-bearing area of the lower leg and the fall in foot vein pressure during exercise. Br J Surg. 1981;(68):297–300. doi: 10.1002/bjs.1800680502.

57. Herouy Y., May A.E., Pornschlegel G., Stetter C., Grenz H., Preissner K.T., Schopf E., Norgauer J., Vanscheidt W. Lipodermatosclerosis is characterized by elevated expression and activation of matrix metalloproteinases: Implications for venous ulcer formation. J Investig Dermatol. 1998;(111):822–827. doi: 10.1046/j.1523–1747.1998.00369.x.

58. Norgauer J., Hildenbrand T., Idzko M., Panther E., Bandemir E., Hartmann M., Vanscheidt W., Herouy Y. Elevated expression of extracellular matrix metalloproteinase inducer (CD147) and membrane-type matrix metalloproteinases in venous leg ulcers. Br J Dermatol. 2002;(147):1180–1186. doi. 10.1046/j.1365–2133.2002.05025.x.

59. Shoab S.S., Porter J.B., Scurr J.H., Coleridge-Smith P.D. Effect of oral micronized purified flavonoid fraction treatment on leukocyte adhesion molecule expression in patients with chronic venous disease: A pilot study. J Vasc Surg. 2000;31 (3):456–461. Available at: https://www.ncbi.nlm.nih.gov/pubmed/10709057.

60. Pappas P.J., You R., Rameshwar P., Gorti R., DeFouw D.O., Phillips C.K., Padberg F.T. Jr., Silva M.B. Jr., Simonian G.T., Hobson R.W., 2nd et al. Dermal tissue fibrosis in patients with chronic venous insufficiency is associated with increased transforming growth factor-beta1 gene expression and protein production. J Vasc Surg. 1999;30:1129–1145. doi: 10.1016 / S 0741–5214 (99) 70054–6.

61. Ackerman Z., Seidenbaum M., Loewenthal E., Rubinow A. Overload of iron in the skin of patients with varicose ulcers. Possible contributing role of iron accumulation in progression of the disease. Arch Dermatol. 1988;124:1376–1378. Available at: https://jamanetwork.com/journals/jamadermatology/article-abstract/549782.

62. Martinez-Zapata M.J., Vernooij R.W., Uriona Tuma S.M., Stein A.T., Moreno R.M., Vargas E., Capella D., Bonfill Cosp X. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2016,4: CD003229. doi: 10.1002/14651858.CD003229.pub3.

63. Katsenis K. Micronized purified flavonoid fraction (MPFF): A review of its pharmacological effects, therapeutic efficacy and benefits in the management of chronic venous insufficiency. Curr Vasc Pharmacol. 2005;3:1–9. Available at: https://www.ncbi.nlm.nih.gov/pubmed/15641940.

64. Bush R., Comerota A., Meissner M., Raffetto J.D., Hahn S.R., Freeman K. Recommendations for the medical management of chronic venous disease: The role of Micronized Purified Flavanoid Fraction (MPFF). Phlebology. 2017;32:3–19. doi: 10.1177/0268355517692221.

65. Kakkos S.K., Nicolaides A.N. Efficacy of micronized purified flavonoid fraction Daflon®on improving individual symptoms, signs and quality of life in patients with chronic venous disease: A systematic review and meta-analysis of randomized double-blind placebo-controlled trials. Int Angiol. 2018;37:143–154. doi: 10.23736/S0392–9590.18.03975–5.

66. Boudet C., Peyrin, L. Comparative effect of tropolone and diosmin on venous COMT and sympathetic activity in rat. Arch Int Pharmacodyn Ther. 1986;283:312–320. Available at: https://www.ncbi.nlm.nih.gov/pubmed/3789890.

67. Savineau J.P., Marthan R. Diosmin-induced increase in sensitivity to Ca2+ of the smooth muscle contractile apparatus in the rat isolated femoral vein. Br J Pharmacol. 1994;111:978–980. doi: 10.1111/j.1476–5381.1994.tb14838.x.

68. Juteau N., Bakri F., Pomies J., Foulon C., Rigaudy P., Pillion G., Lange G., Genre O., Cron J.P. The human saphenous vein in pharmacology: Effect of a new micronized flavonoid fraction (Daflon 500 mg) on norepinephrine induced contraction. Int Angiol. 1995;14:8–13. Available at: https://www.ncbi.nlm.nih.gov/pubmed/8919257.

69. Barbe R., Amiel M. Pharmacodynamic properties and therapeutic efficacy of Daflon 500 mg. Phlebology. 1992;7:41–44.

70. Ibegbuna V., Nicolaides A.N., Sowade O., Leon M., Geroulakos G. Venous elasticity after treatment with Daflon 500 mg. Angiology. 1997;48:45–49. doi: 10.1177/000331979704800108.

71. Friesenecker B., Tsai A.G., Instaglietta M. Capillary perfusion during ischemia-reperfusion in subcutaneous connective tissue and skin muscle. Am J Physiol. 1994;267: H2204 – H2212. doi: 10.1152/ajpheart.1994.267.6.H2204.

72. Friesenecker B., Tsai A.G., Allegra C., Intaglietta M. Oral administration of purified micronized flavonoid fraction suppresses leukocyte adhesion in ischemia-reperfusion injury: In vivo observations in the hamster skin fold. Int J Microcirc Clin Exp. 1994;14:50–55. Available at: https://www.ncbi.nlm.nih.gov/pubmed/7960444.

73. Korthuis R.J., Gute D.C. Postischemic leukocyte / endothelial cell interactions and microvascular barrier dysfunction in skeletal muscle: Cellular mechanisms and effect of Daflon 500 mg. Int J Microcirc Clin Exp. 1997;17:11–17. Available at: https://www.ncbi.nlm.nih.gov/pubmed/9477039.

74. Takase S., Lerond L., Bergan J.J., Schmid-Schonbein G.W. The inflammatory reaction during venous hypertension in the rat. Microcirculation. 2000;7:41–52. Available at: https://www.ncbi.nlm.nih.gov/pubmed/10708336.

75. Pascarella L., Lulic D., Penn A.H., Alsaigh T., Lee J., Shin H., Kapur V., Bergan J.J., Schmid-Schonbein G.W. Mechanisms in experimental venous valve failure and their modification by Daflon 500 mg. Eur J Vasc Endovasc Surg. 2008;35:102–110. doi: 10.1016/j.ejvs.2007.08.011.

76. Takase S., Pascarella L., Lerond L., Bergan J.J., Schmid-Schonbein G.W. Venous hypertension, inflammation and valve remodeling. Eur J Vasc Endovasc Surg. 2004;28:484–493. doi: 10.1016/j.ejvs.2004.05.012.

77. Das Gracas C.D.S.M., Cyrino F.Z., de Carvalho J.J., Blanc-Guillemaud V., Bouskela E. Protective Effects of Micronized Purified Flavonoid Fraction (MPFF) on a Novel Experimental Model of Chronic Venous Hypertension. Eur J Vasc Endovasc Surg. 2018;55:694–702. doi: 10.1016/j.ejvs.2018.02.009.

78. Bogachev V.Y., Boldin B.V., Lobanov V.N. Benefits of micronized purified flavonoid fraction as adjuvant therapy on inflammatory response after sclerotherapy. Int Angiol. 2018;37:71–78. doi: 10.23736/S0392–9590.17.03868–8.

79. Pietrzycka A., Kozka M., Urbanek T., Stpniewski M., Kucharzewski M. Effect of Micronized Purified Flavonoid Fraction Therapy on Endothelin-1 and TNF-alpha Levels in Relation to Antioxidant Enzyme Balance in the Peripheral Blood of Women with Varicose Veins. Curr Vasc Pharmacol. 2015;13:801–808. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26311575.

80. Wali M.A., Suleiman S.A., Kadoumi O.F., Nasr M.A. Superoxide radical concentration and superoxide dismutase (SOD) enzyme activity in varicose veins. Ann Thorac Cardiovasc Surg. 2002;8:286–290. Available at: https://www.ncbi.nlm.nih.gov/pubmed?filters=&orig_db=PubMed&cmd=Search&term=Ann%20Thorac%20Cardiovasc%20Surg%5Bjour%5D%20AND %208%5Bvolume%5D%20AND %20286%5Bpage%5D.

81. Shoab S.S., Porter J., Scurr J.H., Coleridge-Smith P.D. Endothelial activation response to oral micronized flavonoid therapy in patients with chronic venous diseasea prospective study. Eur J Vasc. Endovasc Surg. 1999;17:313–318. doi: 10.1053/ejvs.1998.0751.

82. Shoab S.S., Scurr J.H., Coleridge-Smith P.D. Plasma VEGF as a marker of therapy in patients with chronic venous disease treated with oral micronised flavonoid fraction – A pilot study. Eur J Vasc. Endovasc Surg. 1999;18:334–338. doi: 10.1053/ejvs.1999.0890.

83. Laurent R., Gilly R., Frileux C. Clinical evaluation of a venotropic drug in man. Example of Daflon 500 mg. Int Angiol. 1988;7:39–43. Available at: https://www.ncbi.nlm.nih.gov/pubmed/3053942.

84. Blume J., Langenbahn H., Champvallins M. Quantification of edema using the volometer technique; therapeutic application of Daflon 500 mg in chronic venous insufficiency. Phlebology. 1992;7:37–40.

85. Allaert F.A. Meta-analysis of the impact of the principal venoactive drugs agents on malleolar venous edema. Int Angiol. 2012;31:310–315. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22801396.

86. Tsukanov Y.T., Nikolaichuk A.I. Orthostatic-loading-induced transient venous refluxes (day orthostatic loading test), and remedial effect of micronized purified flavonoid fraction in patients with telangiectasia and reticular vein. Int Angiol. 2017;36:189–196. doi: 10.23736/S0392–9590.16.03708–1.

87. Tsukanov Y.T., Tsukanov A.Y. Diagnosis and treatment of situational great saphenous vein reflux in daily medical practice. Phlebolymphology. 2017; 24:144–151. Available at: https://www.phlebolymphology.org/diagnosis-and-treatment-of-situationalgreat-saphenous-vein-reflux-in-daily-medical-practice/.

88. Behar A., Lagrue G., Cohen-Boulakia F., Baillet J. Study of capillary filtration by double labelling I131-albumin and Tc99m red cells. Application to the pharmacodynamic activity of Daflon 500 mg. Int Angiol. 1988;7:35–38. Available at: https://www.ncbi.nlm.nih.gov/pubmed/3053941.

89. Belcaro G., Cesarone M.R., de Sanctis M.T., Incandela L., Laurora G., Fevrier B., Wargon C., De Gregoris P. Laser Doppler and transcutaneous oximetry: Modern investigations to assess drug efficacy in chronic venous insufficiency. Int J Microcirc Clin Exp. 1995;15:45–49. Available at: https://www.ncbi.nlm.nih.gov/pubmed/8748889.

90. Galley P., Thiollet M. A double-blind, placebo-controlled trial of a new veno-active flavonoid fraction (S 5682) in the treatment of symptomatic capillary fragility. Int Angiol. 1993;12:69–72. Available at: https://www.ncbi.nlm.nih.gov/pubmed/8376915.

91. Paysant J., Sansilvestri-Morel P., Bouskela E., Verbeuren T.J. Different flavonoids present in the micronized purified flavonoid fraction (Daflon 500 mg) contribute to its anti-hyperpermeability effect in the hamster cheek pouch microcirculation. Int Angiol. 2008;27:81–85. Available at: https://www.ncbi.nlm.nih.gov/pubmed/18277344.

92. De Souza M., Cyrino F.Z., Mayall M.R., Virgini-Magalhaes C.E., Sicuro F.L., de Carvalho J.J., Verbeuren T.J., Bouskela E. Beneficial effects of the micronized purified flavonoid fraction (MPFF, Daflon®500 mg) on microvascular damage elicited by sclerotherapy. Phlebology. 2016;31:50–56. doi: 10.1177/0268355514564414.

93. Guilhou J.J., Dereure O., Marzin L., Ouvry P., Zuccarelli F., Debure C., Van Landuyt H., Gillet-Terver M.N., Guillot B., Levesque H., Mignot J., Pillion G., Février B., Dubeaux D. Efficacy ofDaflon 500mg in venous leg ulcer healing: Adouble-blind, randomized, controlled versus placebo trial in 107 patients. Angiology. 1997;48:77–85. doi: 10.1177/000331979704800113.

94. Glinski W., Chodynicka B., Roszkiewicz J., Bogdanowski T., Lecewicz-Torun B., Kaszuba A., Bowszyc J., Nowak A., Wnorowski J., Wa˛sik F., M. Glińska-Ferenz., M. Błaszczyk, P. Strzyga, R. Pachocki. The Beneficial Augmentative Effect of Micronised Purified Flavonoid Fraction (MPFF) on the Healing of Leg Ulcers: An Open, Multicentre, Controlled, Randomised Study. Phlebology. 1999;14:151–157. doi: 10.1177/026835559901400405.

95. Roztocil K., Stvrtinova V., Strejcek J. Efficacy of a 6-month treatment with Daflon 500 mg in patients with venous leg ulcers associated with chronic venous insufficiency. Int Angiol. 2003;22:24–31. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12771852.

96. Fermoso J., Legido A., Del Pino J., Valiente, R. Therapeutic value of hidrosmin in the treatment of venous disorders of the lower limbs. Curr Ther Res Clin Exp. 1992;52:124–134. doi: 10.1016/S0011-393X(05)80444–8.

97. Planchon B. Insuffisance veineuse et Daflon 500 mg [Venous insufficiency and Daflon 500 mg]. Artères Veines. 2016;9:376–380.

98. Gilly R., Pillion G., Frileux C. Evaluation of a new venoactive micronized flavonoid fraction (S 5682) in symptomatic disturbances of the venolymphatic circulation of the lower limb: A doubleblind, placebo-controlled study. Phlebology. 1994;9:67–70. doi: 10.1177/026835559400900206.

99. Jantet G. Chronic venous insufficiency: Worldwide results of the RELIEF study. Reflux assEssment and quaLity of lIfe improvEment with micronized Flavonoids. Angiology. 2002;53:245–256. doi: 10.1177/000331970205300301.

100. Rabe E., Agus G.B., Roztocil K. Analysis of the effects of micronized purified flavonoid fraction versus placebo on symptoms and quality of life in patients suffering from chronic venous disease: From a prospective randomized trial. Int Angiol. 2015;34:428–436. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25972136.

101. Kauss T., Moynet D., Rambert J., Al-Kharrat A., Brajot S., Thiolat D., Ennemany R., Fawaz F., Mossalayi M.D. Rutoside decreases human macrophage-derived inflammatory mediators and improves clinical signs in adjuvant-induced arthritis. Arthritis Res Ther. 2008;10: R19. doi: 10.1186/ar2372.

102. Nikfarjam B.A., Adineh M., Hajiali F., Nassiri-Asl M. Treatment with Rutin-A Therapeutic Strategy for Neutrophil-Mediated Inflammatory and Autoimmune Diseases-Anti-inflammatory Effects of Rutin on Neutrophils. J Pharmacopunct. 2017;20:52–56. doi: 10.3831/KPI.2017.20.003.

103. Cloarec M., Clément R., Griton P. A double-blind clinical trial of hydroxyethylrutosides in the treatment of the symptoms and signs of chronic venous insufficiency. Phlebology. 1996;11:76–82. doi: 10.1177/026835559601100210.

104. Kriner E., Braun R., Hirche H., Van Laak H. Treatment of venous insufficiency. A double-blind trial with Phlebodril. Z Allg. 1985;61:309–313.

105. MacLennan W.J., Wilson J., Rattenhuber V., Dikland W.J., Vanderdonckt J., Moriau M. Hydroxyethylrutosides in elderly patients with chronic venous insufficiency: Its efficacy and tolerability. Gerontology. 1994;40:45–52. doi: 10.1159/000213574.

106. Vanscheidt W., Rabe E., Naser-Hijazi B., Ramelet A.A., Partsch H., Diehm C., Schultz-Ehrenburg U., Spengel F., Wirsching M., Gotz V., et al. The efficacy and safety of a coumarin- / troxerutin-combination (SB-LOT ) in patients with chronic venous insufficiency: A double blind placebo-controlled randomized study. VASA. 2002;31:185–190. doi: 10.1024/0301–1526.31.3.185.

107. Balmer A., Limoni C. Clinical, placebo-controlled double-blind study of venoruton in the treatment of chronic venous insufficiency. Importance of the selection of patients. VASA. 1980;9:76–82. Available at: https://www.ncbi.nlm.nih.gov/pubmed/7368843.

108. Beyer J., Meissner K.O., Happ J., Cordes U. Effect of calcium dobesilate on permeation of plasma proteins in diabetic patients. Dtsch Med Wochenschr. 1980;105:1604–1608. doi: 10.1055/s-2008–1070921.

109. Heidrich H., Gerke E., Nekarda H. Platelet aggregation inhibition with calcium dobesilate. Arzneim Forsch. 1983;33:580–582. Available at: https://www.ncbi.nlm.nih.gov/pubmed/6683538.

110. Benarroch I.S., Brodsky M., Rubinstein A., Viggiano C., Salama E.A. Treatment of blood hyperviscosity with calcium dobesilate in patients with diabetic retinopathy. Ophthalmic Res. 1985;17:131–138. doi: 10.1159/000265364.

111. Suschek C., Kolb H., Kolb-Bachofen V. Dobesilate enhances endothelial nitric oxide synthase-activity in macro- and microvascular endothelial cells. Br J Pharmacol. 1997;122:1502–1508. doi: 10.1038/sj.bjp.0701512.

112. Falkay G., Kovacs L,; Koltringer P., Eber O., Rothlauer W., Klima G., Lind P., Langsteger W., Wakonig P. Calcium dobesilate (Doxium) as a prostaglandin synthetase inhibitor in pregnant human myometrium in vitro Calcium dobesilate and its effects on hemorheology and microcirculation. Experientia. 1984;40:190–191. doi: 10.1007/bf01963593.

113. Casley-Smith J.R. A double-blind trial of calcium dobesilate in chronic venous insufficiency. Angiology. 1988;39:853–857. doi: 10.1177/000331978803901001.

114. Rabe E., Jaeger K.A., Bulitta M., Pannier F. Calcium dobesilate in patients suffering from chronic venous insufficiency: A double-blind, placebo-controlled, clinical trial. Phlebology. 2011;26:162–168. doi: 10.1258/phleb.2010.010051.

115. Widmer L., Biland L., Barras J.P. Doxium 500 in chronic venous insufficiency: A double-blind placebo controlled multicentre study. Int Angiol. 1990;9:105–110. Available at: https://www.ncbi.nlm.nih.gov/pubmed/2254672.

116. Martinez-Zapata M.J., Moreno R.M., Gich I., Urrutia G., Bonfill X. A randomized, double-blind multicenter clinical trial comparing the efficacy of calcium dobesilate with placebo in the treatment of chronic venous disease. Eur J Vasc Endovasc Surg. 2008;35:358–365. doi: 10.1016/j.ejvs.2007.08.012.

117. Coccheri S., Mannello F. Development and use of sulodexide in vascular diseases: Implications for treatment. Drug Des Dev Ther. 2013;8:49–65. doi: 10.2147/DDDT.S6762.

118. Broekhuizen L.N., Lemkes B.A., Mooij H.L., Meuwese M.C., Verberne H., Holleman F., Schlingemann R.O., Nieuwdorp M., Stroes E.S., Vink H. Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus. Diabetologia. 2010;53:2646–2655. doi: 10.1007/s00125-010-1910-x.

119. Mannello F., Ligi D., Raffetto J.D. Glycosaminoglycan sulodexide modulates inflammatory pathways in chronic venous disease. Int Angiol. 2014;33:236–242. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24936532.

120. Fracasso A., Baggio B., Masiero M., Bonfante L., Bazzato G., Feriani M., Gambaro G. Effect of oral treatment with the glycosaminoglycan sulodexide on peritoneal transport in CAPD patients. Perit Dial Int. 2003;23:595–599. Available at: http://www.pdiconnect.com/content/23/6/595.extract.

121. Ciszewicz M., Polubinska A., Antoniewicz A., Suminska-Jasinska K., Breborowicz A. Sulodexide suppresses inflammation in human endothelial cells and prevents glucose cytotoxicity. Transl Res. 2009;153:118–123. doi: 10.1016/j.trsl.2008.12.007.

122. Pletinck A., Van Landschoot M., Steppan S., Laukens D., Passlick-Deetjen J., Vanholder R., van Biesen W. Oral supplementation with sulodexide inhibits neo-angiogenesis in a rat model of peritoneal perfusion. Nephrol Dial Transplant. 2012;27:548–556. doi: 10.1093/ndt/gfr370.

123. Karon J., Polubinska A., Antoniewicz A.A., Suminska-Jasinska K., Breborowicz A. Anti-inflammatory effect of sulodexide during acute peritonitis in rats. Blood Purif. 2007;25:510–514.

124. Mannello F., Ligi D., Canale M., Raffetto J.D. Sulodexide down-regulates the release of cytokines, chemokines, and leukocyte colony stimulating factors fromhumanmacrophages: Role of glycosaminoglycans in inflammatory pathways of chronic venous disease. Curr Vasc Pharmacol. 2014;12:173–185. doi: 10.2174/1570161111666131126144025.

125. Ligi D., Mosti G., Croce L., Raffetto J.D., Mannello F. Chronic venous disease – Part I: Inflammatory biomarkers in wound healing. Biochim Biophys Acta. 2016;1862:1964–1974. doi: 10.1016/j.bbadis.2016.07.018.

126. Mannello F., Medda V., Ligi D., Raffetto J.D. Glycosaminoglycan sulodexide inhibition of MMP-9 gelatinase secretion and activity: Possible pharmacological role against collagen degradation in vascular chronic diseases. Curr Vasc Pharmacol. 2013;11:354–365. doi: 10.2174/1570161111311030010.

127. Ligi D., Mosti G., Croce L., Raffetto J.D., Mannello F. Chronic venous disease-Part II: Proteolytic biomarkers in wound healing. Biochim Biophy. Acta. 2016;1862:1900–1908. doi: 10.1016/j.bbadis.2016.07.011.

128. Urbanek T., Zbigniew K., Begier-Krasinska B., Baum E., Breborowicz A. Sulodexide suppresses inflammation in patients with chronic venous insufficiency. Int Angiol. 2015;34:589–596. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26044841.

129. Saviano M., Maleti O., Liguori L. Double-blind, double-dummy, randomized, multi-centre clinical assessment of the efficacy, tolerability and dose-effect relationship of sulodexide in chronic venous insufficiency. Curr Med Res Opin. 1993;13: 96–108. doi: 10.1185/03007999309111538.

130. Elleuch N., Zidi H., Bellamine Z., Hamdane A., Guerchi M., Jellazi N. Sulodexide in Patients with Chronic Venous Disease of the Lower Limbs: Clinical Efficacy and Impact on Quality of Life. Adv Ther. 2016;33:1536–1549. doi: 10.1007/s12325-016-0359–9.

131. Coccheri S., Scondotto G., Agnelli G., Aloisi D., Palazzini E., Zamboni V. Randomised, double blind, multicentre, placebo controlled study of sulodexide in the treatment of venous leg ulcers. Thromb Haemost. 2002;87:947–952. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12083500.

132. Scondotto G., Aloisi D., Ferrari P., Martini L. Treatment of venous leg ulcers with sulodexide. Angiology. 1999;50:883–889. doi: 10.1177/000331979905001102.

133. Gonzalez Ochoa A. Sulodexide and phlebotonics in the treatment of venous ulcer. Int Angiol. 2017;36:82–87. doi: 10.23736/S0392–9590.16.03718–4.

134. Wu B., Lu J., Yang M., Xu T. Sulodexide for treating venous leg ulcers. Cochrane Database Syst Rev. 2016;2 (6):CD010694. doi: 10.1002/14651858.CD010694.pub2.

135. Lee B.B., Nicolaides A.N., Myers K., Meissner M., Kalodiki E., Allegra C., Antignani P.L., Baekgaard N., Beach K., Belcaro G., et al. Venous hemodynamic changes in lower limb venous disease: The UIP consensus according to scientific evidence. Int Angiol. 2016;35:236–352. Available at: https://www.researchgate.net/publication/299432655_Venous_hemodynamic_changes_in_lower_limb_venous_disease_The_UIP_consensus_according_to_scientific_evidence.

136. Nicolaides A., Kakkos S., Eklof B., Perrin M., Nelzen O., Neglen P., Partsch H., Rybak Z. Management of chronic venous disorders of the lower limbs – guidelines according to scientific evidence. Int Angiol. 2014;33:87–208. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24780922.

137. Gloviczki P., Comerota A.J., Dalsing M.C., Eklof B.G., Gillespie D.L., Gloviczki M.L., Lohr J.M., McLafferty R.B., Meissner M.H., Murad M.H., Padberg F.T., Pappas P. J., Passman M.A., Raffetto J.D., Vasquez M.A., Wakefield T.W. The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2011;53:2S – 48S. doi: 10.1016/j.jvs.2011.01.079.


Для цитирования:


Богачев В.Ю., Мансилья А., Болдин Б.В., Родионов С.В., Дженина О.В. Патогенетическое обоснование флеботропной терапии хронических заболеваний вен. Стационарозамещающие технологии: Амбулаторная хирургия. 2019;(3-4):19-33. https://doi.org/10.21518/1995-1477-2019-3-4-19-33

For citation:


Bogachev V.Y., Mansilla A., Boldin B.V., Rodionov S.V., Dzhenina O.V. Pathogenetic substantiation of phlebotropic therapy for chronic venous diseases. Нospital-replacing technologies:Ambulatory surgery. 2019;(3-4):19-33. (In Russ.) https://doi.org/10.21518/1995-1477-2019-3-4-19-33

Просмотров: 249


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 1995-1477 (Print)
ISSN 2658-3542 (Online)