Shoab, S.S.; (2009) Objective assessment of microcirculatory response in venous disease to therapy. Masters thesis , UCL (University College London).

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Abstract

Venous stasis is associated with leucocyte & endothelial activation as well as local growth factor response in chronic venous distasease (CVD). There is no good data on the response of this increased activation to treatment. The theme of this thesis was to show changes in leucocyte/endothelial activation as well as microcirculatory stasis in response to medical, surgical and compression therapy. Thus these may act as objective measures of response to treatment. Vascular endothelial growth factor (VEGF) is being investigated extensively in various arterial scenarios I demonstrated high plasma levels of among patients with CVD for the first time. Levels in patients were about 60% higher (82pg Vs 52 pg in controls). This may represent an (reparative!) angiogenic response existing along with the leucocyte inflammatory response. I used a model of medical treatment (60 days oral flavonoid therapy) and demonstrated significant change in plasma VEGF (50% reduction i.e. 98 pg to 57 pg/dl), ICAM (32%), VCAM (29%) & lactoferrin (36%) levels in patients. Thus I showed that endothelial cell activation (ECA) as well as VEGF might be used as an objective surrogate marker in CVD. I propose that amelioration of endothelial activation may be a mechanism of action for these compounds. I studied the response of these parameters to surgical treatment of varicose veins in 20 patients. I showed that there is an increased plasma lactoferrin at 4 weeks that goes below starting base line levels at 6 months (865 Vs 870 Vs 519). VEGF levels continued to increase (65 Vs 83 Vs 134 pg/dl) in these patients and this may represent vascular remodelling. Although not all of them are easily explainable, the microcirculatory parameters were shown to have a definable response to therapy. I used a new apparatus (Laser capillary anemometer) to assess the response of the velocity of blood in the microvasculature of patients with venous, arterial or mixed disease. I demonstrated that compression increases velocity of blood in the sub-papillary plexus & lower levels of compression (20 mm Hg) are more effective in increasing velocity in patients with mixed disease. This may explain the basis for using compression therapy in these patients. Thus I have shown that various parameters of microcirculation may be used to assess the response to therapy in CVD. Future uses of these findings may include design of new and novel therapeutic approaches and to prognosticate for the development of skin changes and ulceration of the leg in CVD.

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