Found this paper when researching the annulus after my annulus was "popped." This small, limited rodent study is noteworthy for its finding regarding Daflon decreasing "valvular remodeling," specifically of the annulus. No date is provided:
www.europeanvenousforum.org/files/7th_m ... 203;15.pdf
UCSD School of Medicine wrote:
VENOUS HYPERTENSION INDUCED VENOUS INSUFFICIENCY AMELIORATED BY DAFLON® 500MG Luigi Pascarella, M.D.*, Dzenan Lulic B.S.***, Tomas Alsaigh* , Jeffrey Lee *, Vevek Kapur*, Geert Schmid-Schonbein, Ph.D.,* John Bergan, M.D. F.A.C.S *** From the Departments of Bioengineering and Surgery of the UCSD School of Medicine, San Diego, California *Department of Bioengineering, **Department of Surgery ***UCSD School of Medicine
Introduction: Venous reflux is caused by inflammation induced valve re-modeling. This presents a target for pharmacologic therapy.
Objectives: The purpose of this study was to assess by duplex Doppler ultrasound the pharmacologic amelioration of venous insufficiency, valvular reflux and limb edema following induction of venous hypertension by an arteriovenous (a-v) fistula in the Wistar rat.
Methods: The study was designed with 6 groups of animals to be sacrificed at day 1 (Group 1; n= eight) and (Group 2 with treatment , n=eight), at 7 days (Group 3; n=eight) (Group 4 with treatment, n=eight) and at 21 days (Group 5; n=eight) (Group 6 with treatment , n=eight) following the surgery. Twenty four animals in three groups received femoral a-v fistulas and twenty four received 100 mg/kg/day Daflon® 500 mg. Treatment has been administered by gavage 1 day before surgery and during all the study. A group of 4 sham- operated animals has been used as controls.
A Duplex Ultrasound (ATL- Philips HDI 5000 and7-15 MHz transducer Philips Medical Systems, Bothell, WA) was performed for repetitive examinations of the femoral vein, the saphenofemoral junction (SFJ), the saphenous vein and direction of venous flow.
At the end of each time-point the animals were euthanized. Blood samples were drawn to test the protease activity (Enzcheck protease assay, Molecular Probes, Invitrogen, Carlsbad, Ca) The sapheno femoral junctions of the pressurized limb were harvested to compare with the contralateral SFJ. The fresh specimens were frozen in liquid nitrogen and stored at –70°C. Longitudinal sections (7 microns) were cut across the SaphenoFemoral Junction (SFJ) and the valve leaflets with a cryostat at - 23°C, and air dried for 30 minutes.
Tissue sections were studied by a Gomori Trichrome Technique (Richard Allan Scientific Kalamazoo, MI) while leukocyte infiltration (Granulocyte-CD 52, Serotec, Raleigh, NC, Macrophage CD68, Serotec, Raleigh, NC, B Lymphocytes CD45RA, Caltag Burlingame, CA and T Lymphocytes (CD3, Caltag, Burlingame, CA) was investigated by immunofluorescence.
Results: At 21 days, six of eight untreated animals showed ectatic veins in the lower abdomen and in the medial aspect of the operated limb. An increase in thigh and leg circumference due to edema began at 14 days and progressed until sacrifice in untreated animals while treated animals showed significantly less edema. The untreated animals slept with legs elevated. The treated animals did not.
Sixteen limbs were scanned with duplex ultrasound. In a-v fistula limbs the subterminal valve distal to the SFJ showed progressive increase in annulus diameter (p<0.05) and reflux flow began at 7 days. Daflon® 500 mg treatment reduced this reflux markedly. Reverse blood flow velocity distal to the SFJ was found to be progressively augmented in a manner that resembled human saphenofemoral reflux. This reflux flow was significantly decreased in treated animals (p<0.05). Blood flow velocities in the femoral vein, distal to the a-v fistula, showed a progressive increase in reflux throughout all time points and this was reduced by Daflon® 500 mg treatment (p<0.05).
At 21-days, there was a progressive increase in granulocyte and macrophage infiltration in the junction in controls. The macrophage infiltration was significantly reduced in Daflon® 500 mg treated animals (p<0.05), but no significant increase in B and T lymphocyte infiltration in the junction vein wall compared to controls. There was an increase in plasma protease activity in controls that was markedly reduced in treated animals (p<0.05).
Conclusions: Venous hypertension produced by an arteriovenous fistula is associated with an increase in plasma serine proteases but decreased in Daflon® 500 mg treated animals. Sapheno-femoral granulocyte and macrophage infiltration, venous annulus remodeling, and saphenous vein reflux are also significantly decreased under Daflon® 500 mg treatment.
So, in this study, Daflon 500 decreased the following:
Edema
Proteases
Macrophage and granulocyte infiltration
Annulus remodeling
Venous reflux
According to the study, inflammation caused an increase in the size of the annulus which then led to reflux. If the Introduction is true that, "Venous reflux is caused by inflammation induced valve re-modeling," this would help explain why our valves thicken and stiffen. I wonder if T- and B-cells would have infiltrated if the study had lasted longer.
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