T. Khodabandehlou

Evaluation of haemorheological and microcirculatory disturbances in chronic venous insufficiency: activity of Daflon 500 mg.

The use of Daflon 500 mg has been shown to improve venous tone, microvascular permeability, lymphatic activity, and microcirculatory nutritive flow. This study aimed to assess the effects of Daflon 500 mg at a daily dose of 2 tab/day on microcirculatory, haemorheologic parameters, white blood cell counts and neutrophil activation in patients suffering from chronic venous insufficiency (CVI). This was a single-centre double-blind placebo-controlled study comparing two parallel groups of CVI patients who were treated for 2 months with Daflon 500 mg (n = 39) or placebo (n = 38). Evaluations were performed before treatment (D0) and at the end of treatment (D60). Blood samples were drawn from a foot vein before and at the end of a 15-min period of venous hypertension provoked by a cuff inflated to 100 mm Hg. Red blood cell (RBC) deformability was determined by the initial flow rate filtration technique using a Hanss haemorheometer. RBC aggregation was evaluated by a Myrenne aggregometer based on analysis of transmitted light through a blood sample during flow. RBC disaggregation was evaluated by Sefam erythro-aggregometer based on analysis of the backscattered light through a blood sample in a Couette flow. Microcirculatory parameters were assessed by means of laser Doppler fluxmetry and transcutaneous oxymetry measurements and consisted of continuous records of blood flux (BF) and TcPO2 before and during 15 min of venous hypertension. Results are expressed as absolute values at baseline (before stasis) and at the end of stasis, before and after 2 months of treatment. Univariate analysis showed a significant reduction of the stasis-induced RBC aggregation index (Daflon 500 mg: -0.07+/-0.20; placebo: 0.04+/-0.18; mean +/- SD; p = 0.03). Multivariate analysis identified a subset of 5 variables (RBC aggregation, RBC count, microcirculatory BF, amplitude and frequency of vasomotion) that produced a good discrimination model between the two treatments. Linear combination of these 5 variables in 48 patients with complete data showed a significant difference (p < 0.001) between the groups. These changes suggest a protective effect of Daflon 500 mg on the deleterious influence of stasis on microcirculatory (BF) and hemorheologic (RBC aggregation) parameters in CVI patients in comparison to patients receiving placebo.

Role of albumin and fibrinogen on red cell aggregation-disaggregation in diabetes mellitus

It has been shown that the reversible red blood cell aggregation-disaggregation mechanism presents several abnormalities in diabetic patients. This paper presents the results concerning these abnormalities obtained from a more important number of patients. Our proteins has been particulary focused on alterations of plasmatic proteins, namely fibrinogen and albumin

Measurements of Transcutaneous Oxygen Pressure and Changes in Blood Rheology as Markers of Prognosis of Critically Ischemic Limb in Diabetes Mellitus Patients

The aims of this study were to compare variations of the transcutaneous oxygen pressure (TcPO2) and blood rheology in diabetic patients. Diabetic patients with critical limb ischemia were compared with those who were either asymptomatic or had mild peripheral vascular disease (PVD). The results showed a significant decrease in TcPO2 in patients with critical limb ischemia. Low shear rate blood viscosity, red blood cell (RBC) aggregation, plasma viscosity, and fibrinogen level were significantly higher in the group with critical severe limb ischemia. The group with critical limb ischemia was subdivided on the basis of clinical outcomes after 1 year and the prognostic values of these measurements examined. A TcPO2 value of 10 mm Hg was associated with a positive predictive value of 94%. RBC aggregation index and fibrinogen levels offered positive predictive values of 89% and 88%, respectively, when cut off values were derived from means + 1 SD of same parameters in patients with asymptomatic or mild PVD. TcPO2 is useful to follow the deterioration of diabetics with critical limb ischemia.

IMPAIRED FUNCTION OF FIBRINOGEN: CONSEQUENCES ON RED CELL AGGREGATION IN DIABETES MELLITUS

Two aspects regarding to the functional capacity of fibrinogen for aggregating the red cells were studied in both healthy volunteers and diabetic patients. The first one concerns the activation of the plasminogen that is present in the plasma, thereby involving the susceptibility of the plasma fibrinogen to degradation and ultimatly influencing the red cell aggregation characteristics. The second aspect concerns the quality of fibrinogen and its functional capacity for aggregating red cells. This later is carried-out on isolated and purified fibrinogen from plasma. Experiments made by activating the plasminogen suggest that fibrinogen is less degraded in the plasma of diabetic patients. On the other hand, fibrinogen when isolated from plasma samples of diabetics, is found to be distinct from those obtained from healthy volunteers by its aggregative effects.

The Effects of Cyclo 3 Fort Treatment on Hemorheological Disturbances During a Provoked Venous Stasis in Patients with Chronic Venous Insufficiency

The presence of multiple microcirculatory alterations has already been pointed-out in chronic venous insufficiency “CVI” (1–6). In previous studies, we reported impairments in RBC rheologic behaviour which appear in the early uncomplicated stages of this disease (7–8). These impairements were shown, on the other hand, to be exaggerated when using a venous stasis stimulus in patients.

Effects of buflomedil on microvascular disorders in diabetic patients

The aim of this work was to evaluate the effect of buflomedil on hemorheologic, hemodynamic and microcirculatory properties in diabetic patients. Patients were 20 noninsulin-dependent diabetics with distal arteriopathy characterized by chronic hypoxia (transcutaneous oxygen pressure = 25.2 +/- 4.8 mm Hg). They were randomly assigned to two groups for a double-blind study versus placebo. The treatment consisted of a 4-hour intravenous perfusion of 400 mg of buflomedil or placebo as a daily dose during 7 days. Results showed significant improvements in hemodynamic parameters such as post-occlusive peak flow and time to peak flow at the end of buflomedil treatment. In the same manner, the transcutaneous oxygen pressure was found to be significantly increased after buflomedil treatment, whereas there was no modification by placebo. Indeed, red cell aggregation was significantly less important as a result of buflomedil treatment whilst red cell deformability was found to be significantly increased. These hemorheological improvements make the blood flow redistribution through the microcirculatory network easier and lead ultimately to better tissue oxygenation.

Fibrinolytic and biochemical factors in patients with venous insufficiency

Long-term metabolic changes in vein tissue of the limbs and feet have been reported in the course of chronic venous insufficiency (CVI). Low fibrinolytic potential was first demonstrated using fibrin-embedded vein rings (Todds biopsy), then in blood via increased euglobulin lysis time. This defect is especially pronounced when blood is taken from foot veins of patients with grades 5 and 6 of CVI or skin lesions. Haemorrheological disorders such as increased blood viscosity and red cell aggregation, related mainly to high fibrinogen levels, have also been shown in patients with CVI. Such disorders, particularly observed in blood from foot veins, play an important role in the interaction between the blood cell components and the vessel wall. More recently, the margination and adhesion of white cells to the endothelium and the subsequent activation of white cells have been assumed. Adhesion molecules such as ICAM-1, VCAM-1 and P-selectin have been identified surrounding skin ulceration. There is also evidence that markers of neutrophil degranulation reach high levels in blood taken from foot veins after exposure to experimental venous hypertension. White cell activation results in elevated plasma levels of L-selectin, increased production of oxygen free radicals, pseudopods, CD11b integrin, platelet-monocyte aggregates and abnormal lymphocyte L-selectin. Increased nitric oxide, presumably due to monocyte activation, as well as increased urine haemosiderin related to skin microvessel leakage have also been reported. VCAM-1 and metalloproteinase MMP9 activity have been stated as sensitive markers in relation to endothelium activation and white cell trapping, which follows hypoxia and/or alterations in wall shear stress, mainly in skin venulae and in the region of valves.

Effects of Venous Stasis on Blood Viscosity, Micro-Circulatory Dynamic, Cutaneous Oxygen Pressure

Numerous works have pointed-out the hemorheologic disorders which occur in patients with chronic venous insufficiency “CVI” (1,2,3). It was also demonstrated that the cutaneous blood flux and vasomotion are disturbed during this pathology (4,5). Disturbances caused by the disease occur mainly in stasis areas (1) and are accompanied by a tissue hypoxia.

S11.3. Relationship between transcutaneous oxygen pressure and hemorheology in diabetes mellitus

Diabetes is associated with altered blood viscosity and abnormal tissue oxygenation. Transcutaneous oxygen tension is measured in 119 diabetic and 20 normal subjects. Measurements of transcutaneous oxygen pressure (TcPO2) are made by Oxymonitor SM 361 at 45 degrees C at the dorsum of the foot. At the same time, the main microrheological parameters (plasma viscosity, albumin, fibrinogen, red cell aggregation times, disaggregation threshold and red cell aggregate structure index) are measured in diabetic patients with good and poor glycemic control, with and without angiopathy. All the diabetics have a significant reduction of TcPO2 and have rheological disturbances. TcPO2 values are related significantly with plasma viscosity and with several parameters of aggregation-disaggregation phenomenon. As for microrheological parameter abnormalities, it seems that tissue hypoxia precedes clinical signs of angiopathy and depends on the metabolic state as rheological abnormalities. TcPO2 values are the result of numerous parameters as rheological parameters. It seems that TcPO2 measurement is able to provide useful informations about microcirculation in diabetes mellitus without clinical signs of tissue hypoxia.