Effects of chlorpromazine and methylprednisolone on perfusion preservation of rabbit livers

Abstract

The isolated perfused rabbit liver was used to determine how continuous hypothermic perfusion affected liver function. Rabbit livers were perfused for 0, 24, 48, and 72 hr at 5 °C with the UW perfusate containing hydroxyethyl starch (5 g%) dissolved in a solution containing gluconate (80 m M), adenosine (5 m M), glutathione (3 m M), phosphate (25 m M), and additives as described previously, and they were used successfully for kidney preservation. At the end of preservation the livers were perfused in an isolated circuit with a Krebs-Henseleit solution with addition of 4 g% bovine serum albumin and 10 m M glucose at 38 °C for 120 min. Bile was collected from the cannulated common duct. Biliary excretions of indocyanine green and liver enzymes lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase, were determined both in the cold perfusate and the normothermic perfusate. Livers were also studied after pretreatment of the donor with Chlorpromazine (CPZ) and/or methylprednisolone (MP). Bile production (ml/120 min, 100 g liver) upon reperfusion produced the most interesting data and decreased from a control value of 10.3 ± 2.6 to 9.3 ± 1.0 (24 hr), 5.3 ± 0.7 (48 hr), and 4.1 ± 1.5 (72 hr). Enzyme release was not predictive of the degree of preservation-induced damage. Pretreatment of rabbits with a combination of CPZ/MP improved bile flow at 48 and 72 hr (8.3 ± 3.0 and 7.0 ± 1.3, P < 0.05). Pretreatment with either drug alone also improved function after 72 hr of preservation (7.1 ± 1.8, CPZ; 8.2 ± 3.5, MP). These results demonstrate that liver function can be successfully preserved during continuous hypothermic perfusion for 48 hr and possibly 72 hr with the UW perfusion fluid as tested in the isolated perfused liver model. CPZ and MP pretreatment appear necessary to prevent preservation-induced damage.