Hepatotoxic effects of polidocanol in a model of autologously perfused porcine livers

Abstract

Polidocanol is an effective sclerosing agent that consists of 95% hydroxypolyethoxydodecane and 5% ethyl alcohol and is known to have a low risk of complications. However, since the compound has been proposed for the local treatment of liver diseases, the potential for topical hepatic side effects should be examined. Therefore, the new model of normothermic-hemoperfused isolated porcine slaughterhouse livers was used to examine polidocanol-hepatotoxicity encompassing the advantages of slaughterhouse organs to reduce animal experiments and autologous blood as an optimal perfusate. Polidocanol was administered via the hepatic artery and portal vein and the effects of the sclerosant on organ function parameters were compared with those in an untreated control group. In contrast to the untreated control organs, significant differences were found in the polidocanol group for parameters such as alanine aminotransferase or organ weight after perfusion. The most striking differences were found for hepatic bile flow, which dropped in the polidocanol group to 0.24+/-0.02 ml/min per 1000 g after administration of the compound compared with 3.80+/-1.08 ml/min per 1000 g in the control group. In summary, the present observations indicate a risk of hepatotoxic effects of polidocanol. Clinicians should be aware of this problem and the use of polidocanol for intrahepatic sclerosing should be restricted to specialized centers.

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“…The perfusion system consisted of separated blood and dialysis circuits as described [2], that may also be used for the perfusion of other organs and tissues, like the liver [39,40], the heart [41] or the skin [38]. The volume of heparinized (20.000 IE/l) blood was 600 ml, added with standard electrolyte solution (modified Tyrode's solution) to adjust pressures and hemoglobin concentration and to replace urine fluid loss.…”

Haemoperfused liver as an ex vivo model for organ invasion of Candida albicans

“…To set up our perfusion model, four livers were perfused for 3 h without the application of fungal cells. Perfusion was carried out as described previously (Grosse-Siestrup et al, 2002b, 2004 with modifications ( Fig. 1).…”

“…The connected liver was put into a sterile plastic bag to create a humid atmosphere and placed on a waterbed kept at 37 uC. Perfusion parameters were adjusted and maintained as described previously (Grosse-Siestrup et al, 2002b, 2004. During perfusion, samples of blood and dialysate were taken periodically for standard clinical laboratory analysis, as described previously (Grosse-Siestrup et al, 2002b, 2004.…”

“…Perfusion parameters were adjusted and maintained as described previously (Grosse-Siestrup et al, 2002b, 2004. During perfusion, samples of blood and dialysate were taken periodically for standard clinical laboratory analysis, as described previously (Grosse-Siestrup et al, 2002b, 2004. This included determination of the concentrations of the marker enzymes ALT and aspartate aminotransferase (AST) in the blood.…”

Artificial Circulation of the Liver: Machine Perfusion as a Preservation Method in Liver Transplantation

“…Normothermic perfusion has been studied frequently but only for a short period of time in an isolated organ perfusion system to assess, for example, hepato‐toxic effects of particular compounds (Grosse‐Siestrup et al,2004; Nui et al,2006). The application in preservation was only attempted by a few research groups (Friend et al,2001; Schon et al,2001).…”