thromboxane-a2 and Varicose-Veins

Patients admitted for surgical removal of varicose veins were treated in a blinded manner for 48 hours prior to surgery with either placebo, low-dose aspirin (25 mg twice daily), dipyridamole (150 mg twice daily) or both. Segments of vein excised at surgery were incubated with or without sodium arachidonate and subsequent prostacyclin (PGI2) production was measured without knowledge of treatment given. During the first 5 minute period of incubation in the presence of arachidonate, veins from dipyridamole-treated patients demonstrated increased (by 75%) arachidonate-stimulated PGI2 production compared to placebo-treated patients. By contrast, PGI2 production was reduced by 64% by aspirin treatment and 67% by aspirin plus dipyridamole compared to placebo-treated patients (p = less than 0.05). In unstimulated vein segments incubated in the absence of arachidonate, spontaneous PGI2 production during the first 5 minute incubation period was increased 32% following dipyridamole treatment but was unchanged following aspirin treatment. By contrast, unstimulated (spontaneous) PGI2 production in patients treated with aspirin plus dipyridamole was reduced by 57% (p = less than 0.05), compared to both placebo- and aspirin-treated patients, and by 71% (p = less than 0.05) compared to dipyridamole-treated patients. With repeated change of incubation medium, the ability of vein walls to produce PGI2 declined. This exhaustion was not prevented by drug treatment. However, drug effects between patient treatment groups were consistent over successive incubation periods. These results suggest that certain therapeutic benefits that might be achieved by enhancement of PGI2 production from vascular endothelium following dipyridamole treatment may be reduced by simultaneous aspirin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aspirin; Dipyridamole; Double-Blind Method; Endothelium, Vascular; Epoprostenol; Humans; Prospective Studies; Randomized Controlled Trials as Topic; Saphenous Vein; Thromboxane A2; Varicose Veins

The authors should like to contribute to the unsettled problem of the development of varicose venous disease with their own experience. They evaluate parallel the histomorphological observations and certain pathobiochemical changes which can be recognized in exstirpated varicose veins. Fourty five stripped saphenas have been studied. They were divided into two groups: a macroscopically normal and a varicose one. The varicose patients were divided again into two subsamples according to the occurrence or lack of thrombophlebitis in their medical case history. The authors were looking for the appropriate pathobiochemical changes of the vessel walls running parallel to the usual histopathological changes. It seems quite possible that the effect which triggers the development of the disease could be anything which causes hypoxia, alters the energy metabolism of the otherwise bradytrophic vascular tissues. Accumulation of proteoglycans, as well as collagen and elastic fibers in place of the smooth muscle cells may cause a decrease in the elasticity of the veins and may produce favourable conditions to thrombus formation and local inflammation.

Topics: Carbon Dioxide; Collagen; Elastin; Electron Transport Complex IV; Female; Humans; Lactates; Lactic Acid; Male; Middle Aged; Proteoglycans; Saphenous Vein; Thrombophlebitis; Thromboxane A2; Tissue Plasminogen Activator; Varicose Veins

Increased urinary metabolites of the antiaggregatory vasodilator prostacyclin (PGI2) and the proaggregatory vasoconstrictor thromboxane A2 (TXA2) have been reported in deep vein thrombosis; however, the tissue(s) of origin is uncertain. Because little is known about the formation of PGI2 or TXA2 from its common precursor, prostaglandin (PG) endoperoxide H2 (PGH2), by varicose veins, we determined the formation of 6-keto-PGF1 alpha (the stable metabolite of PGI2), TXB2 (the stable metabolite of TXA2), and PGE2. Segments of normal saphenous vein and varicose vein (nine and six patients, respectively) were incubated with 10 microM [14C]PGH2 for 2 min at 37 degrees C; products were separated by thin-layer chromatography. Surface area and mass of normal and varicose vascular segments were 19.5 +/- 0.8 versus 18.8 +/- 0.6 mm2 and 11.6 +/- 1.4 versus 10.7 +/- 0.7 mg, respectively. Formation of 6-keto-PGF1 alpha and TXB2 by the segments of varicose vein was significantly increased over that of normal vein: 157 +/- 14 versus 243 +/- 17 pmole of 6-keto-PGF1 alpha (P less than 0.005) and 22 +/- 3 versus 35 +/- 5 pmole of TXB2 (P less than 0.01). The formation of PGE2 by segments of varicose vein was not significantly different from that of normal vein (201 +/- 9 vs 219 +/- 11, respectively). Deoxyribonucleic acid (DNA) content of normal and varicose vein was 1.69 +/- 0.12 and 1.51 +/- 0.13 mg per gram of tissue, respectively. The data suggest that the increased PGI2 formation may reflect increased activity or content of PGI2 synthase. The increase in TXA2 formation may reflect increased productivity or an increased presence of residual platelets or microemboli.

Topics: 6-Ketoprostaglandin F1 alpha; Epoprostenol; Humans; Prostaglandin Endoperoxides, Synthetic; Prostaglandin H2; Prostaglandins H; Thromboxane A2; Thromboxane B2; Varicose Veins

In this study, formation of arachidonic acid-derived prostanoids was investigated in saphenous veins of varicosed and nonvaricosed patients, all undergoing saphenectomy respectively for varicosis or in preparation for coronary bypass operation. Venous production of prostacyclin (PGI2), thromboxane A2 (TXA2) and prostaglandin E2 (PGE2) was assessed by bioassay and/or radioimmunologic assays as appropriate. Fragments of saphenous veins from varicosed patients produced significantly less PGI2 and more TXA2 and PGE2 than those from the control patients. Addition of arachidonic acid to incubation mixtures dose dependently increased release of these prostanoids, but the levels of PGI2 produced were consistently lower in veins from varicosed patients. No differences were found in varicosed patients between various segments of the same vein, no matter whether macroscopically affected or unaffected. These results demonstrate that the cyclooxygenase pathway in the venous wall of subjects with varicosis is shifted toward lesser formation of PGI2 and higher production of proaggregatory and proinflammatory prostanoids such as PGE2 and TXA2. These biochemical changes may be relevant to inflammation and thrombogenesis in varicosis.

Topics: Dinoprostone; Epoprostenol; Female; Humans; Male; Middle Aged; Saphenous Vein; Thromboxane A2; Varicose Veins