Time course of microvalve pathophysiology in high pressure low flow model of venous insufficiency and the role of micronized purified flavonoid fraction.

Abstract

The aim of this study was to characterize, in an experimental model, the mechanisms involved in the initiation of venous insufficiency at the level of microvenous valve and whether they can be influenced by early treatment with micronized purified flavonoid fraction (MPFF). The external right iliac vein of 78 male golden Syrian hamsters was ligated to induce chronic venous insufficiency. Internal venular diameter as well as leukocyte-endothelium-interaction (leukocytes sticking after staining with rhodamine 6G), were assessed using an intravital microscope. In the second part of the study 30 animals were divided into three groups and underwent: ligation plus MPFF, ligation plus 10% lactose solution (vehicle), or sham operation. Treatment with MPFF 100 mg/kg/day or vehicle started 2 days before ligation and lasted for 7 days. Venular diameter and number of adherent leukocytes were assessed 5 days post-ligature. Venular diameter increased immediately after ligature and reached a maximum at 4 hours (P<0.001 vs. baseline), followed by a plateau before gradually returning to baseline dimensions. The increase in the number of adherent leukocytes was also immediate but attained maximal number at 3 days (P<0.0001), followed by a plateau and then gradual return to baseline numbers. In MPFF-treated animals, leukocyte adhesion to the microvalves was prevented compared with vehicle-treated animals (P<0.0001) and venular diameter was also significantly reduced (P<0.05). Venous hypertension induced immediate venular dilatation followed by an increase in the number of adherent leukocytes at microvalve level. Treatment with MPFF prevented the initiation of microvalve inflammation and may play a protective role in the progression of chronic venous insufficiency.