EFFECT OF COLD AND WARM ISCHEMIA ON DRUG-METABOLISM IN ISOLATED HEPATOCYTES AND SLICES FROM HUMAN AND MONKEY LIVER

1. The influence of short-term cold storage in University of Wisconsin organ preservation solution (UW) on the ability to metabolize lidocai ne, testosterone and 7-ethoxycoumarin in isolated human and cynomolgus monkey (Macaca fascicularis) hepatocytes and liver slices has been in vestigated. 2. The human liver tissue was obtained from two different sources, i.e. healthy liver tissue from patients undergoing partial he patectomy because of metastases of colorectal carcinoma (PH livers) an d donor tissue remaining as surgical waste after reduced size or split liver transplantation (Tx livers). Tx livers were perfused in situ wi th ice-cold UW avoiding warm ischaemia. This in contrast with PH liver s, where the operation caused warm ischaemia for 5-90 min. 3. Liver sl ices and hepatocytes from cynomolgus monkey liver showed comparable me tabolic rates for the substrates tested, indicating that all hepatocyt es in the slice are participating in the biotransformation of the subs trates. These monkey liver preparations can be stored up to 18 h with only a slight loss of their metabolic capacity. 4. Liver slices and is olated hepatocytes from the Tx livers as well as isolated cells from t he PH livers could also be stored up to Is h without losing metabolic capacity. However, for liver slices prepared from PH livers cold stora ge is not recommended, because metabolic function was reduced by appro ximately 40 % after 18 h.