RESUMO
OBJECTIVES: To characterize the acute response of the vein wall to venous hypertension and associated altered fluid shear stress and to test the effect of micronized purified flavonoid fraction (MPFF, Daflon 500), on this response. MATERIAL AND METHODS: A femoral arteriovenous fistula was created in Wistar rats (n=48). A cohort of 24 rats received oral treatment with MPFF (100 mg/kg/day body weight), 24 rats underwent the arteriovenous fistula procedure and received no treatment. At days 1, 7 and 21 the animals (n=8 at each time point) were killed. Experimental parameters measured included limb circumference, blood flow at the sapheno-femoral junction, leukocyte infiltration and gelatinase activity (matrix metalloproteinase, MMP). RESULTS: The acute rise in venous hypertension was accompanied by limb edema and venous reflux together with an eventual loss of valve leaflets in the saphenous vein. There was an increase in granulocyte and macrophage infiltration into the venous wall and the surrounding tissue, and a lesser increase in T- and B-lymphocyte infiltration. These changes were accompanied by a local increase in the proteolytic enzymes, MMP-2 and MMP-9. Administration of MPFF reduced the edema and lessened the venous reflux produced by the acute arteriovenous fistula. Decreased levels of granulocyte and macrophage infiltration into the valves were also observed compared with untreated animals. CONCLUSIONS: Venous hypertension caused by an arteriovenous fistula resulted in the development of venous reflux and an inflammatory reaction in venous valves culminating in their destruction. MPFF was able to delay the development of reflux and suppress damage to the valve structures in this rat model of venous hypertension.
Assuntos
Fármacos Cardiovasculares/farmacologia , Diosmina/farmacologia , Veia Femoral/efeitos dos fármacos , Veia Safena/efeitos dos fármacos , Insuficiência Venosa/tratamento farmacológico , Pressão Venosa/efeitos dos fármacos , Animais , Derivação Arteriovenosa Cirúrgica , Velocidade do Fluxo Sanguíneo , Fármacos Cardiovasculares/uso terapêutico , Quimiotaxia de Leucócito/efeitos dos fármacos , Diosmina/uso terapêutico , Modelos Animais de Doenças , Edema/etiologia , Edema/fisiopatologia , Edema/prevenção & controle , Artéria Femoral/cirurgia , Veia Femoral/enzimologia , Veia Femoral/patologia , Veia Femoral/fisiopatologia , Veia Femoral/cirurgia , Granulócitos/efeitos dos fármacos , Granulócitos/patologia , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional , Veia Safena/enzimologia , Veia Safena/patologia , Veia Safena/fisiopatologia , Estresse Mecânico , Fatores de Tempo , Insuficiência Venosa/complicações , Insuficiência Venosa/enzimologia , Insuficiência Venosa/patologia , Insuficiência Venosa/fisiopatologiaRESUMO
The influence of buffered media upon the growth and alkaloid productivity of Catharanthus roseus hairy root culture was examined. As expected, the buffers minimized shifts in the pH of the media and had slightly negative effects upon growth. The growth of the hairy roots remained optimal in unbuffered media. The specific yield of lochnericine was significantly lower in response to the addition of buffers, while tabersonine was significantly higher. In contrast, the specific yields of ajmalicine, serpentine, and horhammericine remained unchanged.
