Studies on Vascular Endothelial Cell Damage by Polidocanol in Relation to Concentration, Ethylene‐oxide Chain Length and Exposure Time

Abstract

Abstract: In sclerotherapy for esophageal varices, the mechanism of intravariceal thrombus formation produced by a sclerosant (polidocanol, ethanolamine oleate, etc) is thought to be endothelial cell damage.Polidocanol (polyoxethylene monododecyl ether) has an average ethylene oxide chain length of 9 (ñ= 9) and is a non‐ionic surfactant. The extent of vascular endothelial cell damage is thought to be dependent on (1) the concentration (%) of polidocanol, (2) the length of ethylene oxide chains(n), and (3) the duration of exposure of endothelial cells to the sclerosant. Using these parameters, we evaluated the efficacy of sclerotherapy in two experimental systems employing cultured human endothelial cells and canine mesenteric veins. As the sclerosant concentration was increased, the extent of cell damage became greater, suggesting that thrombus formation can be more effectively induced with a higher concentration of sclerosant. As for the length of the ethylene oxide chains, a sclerosant with ñ=12 showed markedly reduced cytotoxicity as compared to those with ñ= 6 and ñ= 8. Cytotoxicity increased in proportion to the duration of exposure to the sclerosant, suggesting that exposure time is a key determinant of vascular endothelial cell damage. From these results, it is concluded that sclerotherapy for esophageal varices will be more effective if a high concentration of sclerosant is used for large varices with high blood flow, provided that a suitable ethylene oxide chain length is used and that the sclerosant is retained in the varices for 30–60 seconds.