[Microcirculatory consequences of a venous striction in the rat. Effect of a coumarine-rutine association]. / Conséquences microcirculatoires d'une striction veineuse chez le rat. Effet d'une association coumarine-rutine.

The aim of this study was to investigate the consequences of a venous striction on capillary red blood cell distribution and venular blood return and the effect of a coumarin derivative-rutoside combination. The study was conducted, in vivo, in the rat cremaster muscle using intravital microscopy. The striction lasted thirty minutes and was obtained by clamping the epigastric vein. This mechanical constraint was sufficient to induce microcirculatory modifications without disrupting microvessels. Before the striction (t-5 min), the velocities and diameters of the veins and arteries were comparable in all groups. After the striction (t5 min), in the control group, venous blood flow decreased by 60%, from 0.48 +/- 0.09 mm3/s (t-5 min) to 0.20 +/- 0.06 mm3/s (t5 min). The results showed that after thirty minutes reperfusion, venular blood flow in the control animals was only 34% of initial blood flow. The mean red blood cell velocity dropped by 56%, the percentage of low perfused capillaries increased from 7.5% to 50%. Treatment of animals with a coumarin derivative-rutoside combination, particularly at 4 mg/kg coumarin derivative-100 mg/kg rutoside, has significantly improved the microcirculation. After thirty minutes reperfusion venular blood flow was 60% and the percentage of low perfused capillaries was only 10%. The effect seemed to be more pronounced for rutoside than coumarin derivatives. The interest of this study was to set up an experimental model of a venous striction not too severe to induce micro-hemorrages but enough to modify microcirculation. This model was used to quantify the beneficial effects of a coumarin derivative-rutoside combination.

Supplementation with wine phenolic compounds increases the antioxidant capacity of plasma and vitamin E of low-density lipoprotein without changing the lipoprotein Cu(2+)-oxidizability: possible explanation by phenolic location.

OBJECTIVES: To evaluate the effect of the red wine phenolic compound (RWPC) dietary supplementation without alcohol interference on: (1) some of the biochemical characteristics of LDL, (2) the oxidative susceptibility of LDL and (3) the antioxidant capacity of total plasma (Pl-AOC). In order to account for discrepancies between the three series of data, the in vitro stability of the association of phenolic compounds and LDL was tested. DESIGN: An intervention study with 20 volunteers. Each served as his own control. Cu(2+)-oxidizability of LDL and Pl-AOC were tested on blood samples before and after dietary supplementation. Cu(2+)-oxidizability of LDL was also tested by co-incubation in the presence of RWPC or phenolic acids with or without extensive dialysis. SETTING: The Laboratory of Lipid Biochemistry and Biology, School of Medicine, and the Laboratory of Metabolic Diseases, Lapeyronie Hospital, University of Montpellier, France. SUBJECTS: Healthy males, nonsmokers and moderate drinkers, submitted to a dietary regimen deprived of vitamin E and C for a period of 10 d before supplementation. They also abstained from alcohol, wine, fruit juices, coffee, tea and cola beverages during this period. INTERVENTION: Six 0.33 g capsules/d (namely two capsules at each meal) of a preparation of red wine phenolic compounds in a dry powder form were given to the volunteers over a period of two weeks. Blood samples were drawn in fasting conditions at day 0 and day 14 of the supplementation period. RESULTS: Supplementation led to: (1) in LDL, a significant increase in vitamin E content (n = 20, P = 0.01) or vitamin E/total fatty acid bis-allylic carbon number ratio (n = 20, P = 0.006) without modification in the other biochemical characteristics or Cu(2+)-oxidizability; (2) in plasma, a significant increase in the antioxidant capacity (n = 11, P = 0.01). In vitro studies showed that RWPC or sinapic, caffeic or ferulic acids incubated in the presence of LDL increased the protection of the lipoparticle against oxidation (caffeic > sinapic > ferulic). This effect, however, was totally lost after extensive dialysis. CONCLUSIONS: The enhancing effect of the RWPC supplementation on Pl-AOC may be due to a phenolic-compound action both in the aqueous phase of plasma and at the surface of lipoprotein particles. Surface location possibly explains the enhancing-sparing effect of supplementation on LDL vitamin E and the absence of effect on dialysed-LDL oxidizability.

Effect of a combination of coumarin derivatives and rutoside on venous and lymphatic circulations during severe constriction of the caudal vena cava in rabbits.

The effect of a coumarin (CAS 91-64-5) derivatives-rutoside (CAS 153-18-4) combination (Esberiven) has been investigated in an in vivo model of venous hind leg stasis elicited by severe constriction of the caudal vena cava in anesthetized rabbits. The vena cava flow is initially reduced by 80% compared to reference values; then, it significantly declines over time. The venous femoral pressure drops as well as the perfusion pressure whereas the peripheral resistance increases. The popliteal lymph flow gradually slows down after the constriction. Moreover, this venous constriction results in a marked reduction of the right ventricular stroke volume responsible for a left ventricle failure and for the exitus of 30% of the rabbits within 1-3 h post-constriction. A 5-day pretreatment (i.v.) with the coumarin derivatives-rutoside combination at a dose of 4 mg of coumarin derivatives + 200 mg of rutoside/rabbit/day increases the lymph flow but does not suppress the mechanically-induced venous flow decrease. The 6th-day treatment (infusion at the respective doses of 5 mg of coumarin derivatives + 250 mg of rutoside/kg or 10 mg of coumarin derivatives + 500 mg of rutoside/kg) induces a dose-related significant increase of both venous and lymph flows and of the femoral pressure. At the same time, the peripheral venous resistance decreases in a dose-response relationship. Furthermore, after administration of coumarin derivatives and rutoside, the right ventricle stroke volume increases and no death occurs.