Chronic Venous Insufficiency and the Therapeutic Effects of Daflon 500 mg

Abstract

Chronic venous insufficiency is linked to venous hypertension and forces of shear stress on the endothelium. Venous hypertension depends upon two forces: the weight of a column of blood from the right atrium transmitted through the valveless vena cava and iliac veins to the femoral vein, and pressure generated by contracting skeletal muscles of the leg transmitted through failed perforating veins. When valve failure occurs in superficial axial veins and perforating veins, the venous pressure in the veins and venules of the skin and subcutaneous tissue is raised. The skin changes in chronic venous insufficiency are directly related to the severity of the venous hypertension. Also, pathologic changes in the valves are linked to venous hypertension and leukocyte infiltration and activation. It is hypothesized that acute venous pressure elevations cause a shift in the venous hemodynamics with changes in wall shear stress. This initiates the inflammatory cascade. Daflon 500 mg ameliorates the effects of chronic inflammation. In randomized trials, 60 days of therapy with Daflon at a dosage of 500 mg 2 tablets daily was effective, in addition to elastic compression, in accelerating venous ulcer healing. Because venous insufficiency is linked to venous hypertension and an inflammatory reaction, it appears that Daflon 500 mg 2 tablets daily shows a great potential for accomplishing blockade of the inflammatory cascade.

Get full access to this article

View all access options for this article.

References

Nicolaides AN

: Investigation of chronic venous insufficiency: A consensus statement (France, March 5-9, 1997). Circulation 102:E126-E163, 2000.

Takase S

Lerond L

Bergan JJ

et al

: The inflammatory reaction during venous hypertension in the rat. Microcirculation 7:41-52, 2000.

Buján J

Jurado F

Gimeno MJ

et al

: Changes in metalloproteinase (MMP-1, MMP-2) expression in the proximal region of the varicose saphenous vein in young subjects. Phlebology 15:64-70, 2000.

Ono T

Bergan JJ

Schmid-Schönbein GW

et al

: Monocyte infiltration into venous valves. J Vasc Surg 27:158-166, 1998.

Takase S

Schmid-Schönbein G

Bergan JJ

: Leukocyte activation in patients with venous insufficiency. J Vasc Surg 30:148-156, 1999.

Bergan JJ

: Surgical management of primary and recurrent varicose veins. In: Handbook of Venous Disorders, ed. by

Gloviczki P

Yao JST

. London: Chapman and Hall, 1996.

Arnoldi CC

: In: Controversies in the Management of Venous Disorders, ed. by

Eklöf B

Gjöres JE

Thulesius O

et al.

London: Butterworths, 1989, p 13.

Bjordal RI

: Circulation patterns in incompetent perforating veins in the calf and in the saphenous system in primary varicose veins. Acta Chir Scand 138:251-261, 1972.

Hahn TL

Unthank JL

Lalka SG

: Increased hindlimb leukocyte concentration in a chronic rodent model of venous hypertension. J Surg Res 81:38-41, 1999.

10.

Nicolaides AN

Sumner DS

: Ambulatory venous pressure measurements. In: Investigations of Patients with Deep Venous Thrombosis and Chronic Venous Insufficiency, ed. by

Nicolaides AN

Sumner DS.

London: Med-Orion, 1991, pp 29-31.

11.

Pappas PJ

Fallek SR

Garcia A

et al

: Role of leukocyte activation in patients with venous stasis ulcers. J Surg Res 59:553-558, 1995.

12.

Pappas PJ

You R

Rameshwar P

et al

: Dermal tissue fibrosis in patients with chronic venous insufficiency is associated with increased transforming growth factor-1 gene expression and protein production. J Vasc Surg 30:1129-1145, 1999.

13.

Gradman WS

Segalowitz J

Grundfest W

: Venoscopy in varicose vein surgery: Initial Experience. Phlebology 8:145-150, 1993.

14.

Van Cleef JF

Desvaux P

Hugentobler JP

et al

: Endoscopie veineuse. J Mal Vasc 16:184-187, 1991.

15.

Blanchemaison P

: Significance of venous endoscopy in the exploration and the treatment of venous insufficiency of the legs [in French]. J Mal Vasc 17(suppl B):109-112, 1992.

16.

Schmid-Schönbein GW

Takase S

Bergan JJ

: New advances in the understanding of the pathophysiology of chronic venous insufficiency. Angiology 52(suppl 1):S27-S34, 2001.

17.

Simon SI

Goldsmith HL

: Leukocyte adhesion dynamics in shear flow. Ann Biomed Eng 30:315-332, 2002.

18.

Nagel T

Resnick N

Atkinson WJ

et al

: Shear stress selectively upregulates intercellular adhesion molecule-1 expression in cultured human vascular endothelial cells. J Clin Invest 94:885-891, 1994.

19.

Takase S

Pascarella L

Bergan JJ

et al

: Hypertension induced valve remodeling. J Vasc Surg 39:1329-1335, 2004.

20.

Ortega F

Mompeo B

Sarmiento L

et al

: Comparison of saphenous veins removed for primary venous insufficiency with cadaver saphenous veins. Vasc Surg 31:663-670, 1997.

21.

Friesnecker B

Tsai AG

Allegra C

et al

: Oral administration of purified micronised flavonoid fraction suppresses leukocyte adhesion in ischemia-perfusion injury. Int J Microcirc 14:50-55, 1994.

22.

Korthuis RJ

Gute DC

: Post ischemic leukocyte/endothelial cell interactions and microvascular barrier disruption in skeletal muscle: Cellular mechanisms and the effect of Daflon 500 mg. Int J Mirocirc 17(suppl 1):11-17, 1997.

23.

Takase S

Lerond L

Bergan JJ

et al

: Enhancement of reperfusion injury by elevation of microvascular pressures. Am J Physiol Heart Circ 282:H1387-H1394, 2002.

24.

Takase S

Delano FA

Lerond L

et al

: Inflammation in chronic venous insufficiency: Is the problem insurmountable? J Vasc Res 36(suppl 1):3-10, 1999.

25.

Guilhou JJ

Dereure O

Marzin L

et al

: Efficacy of Daflon 500 mg in venous leg ulcer healing: A double-blind, randomized, controlled versus placebo trial in 107 patients. Angiology 48:77-85, 1997.