Effect of drug treatment on liver-slice function following 72-hour hypothermic perfusion

Abstract The viability of hypothermically perfused dog liver was evaluated with a tissue-slice technique. After being preserved for 72 hr, slices of liver were incubated at 30 °C for as long as 2 hr; then water content, K + Na + ratio, and ATP concentration were measured. Dog livers were assigned to the following experimental groups: Group 1 (no preservation; control); Group 2 (livers preserved for 72 hr); Group 3 (donor animals pretreated with 3.5 mg/kg of chlorpromazine (CPZ) and 20 mg/kg of methylprednisolone (MP), and livers preserved for 72 hr); Group 4 (livers pretreated with 2-deoxycoformycin (2-DOC), 50 mg/liter, and preserved for 72 hr); and Group 5 (combination of Group 3 and Group 4 treatments). Livers in Groups 2, 3, and 4 lost K + during preservation, and the mean K + Na + ratio significantly decreased from a control value of 4.2 ± 0.4 to 1.5–1.9 ( P + ; mean K + Na + ratio was 3.9 ± 0.5. Fresh livers (no preservation) rapidly reaccumulated K + when the tissue slices were incubated for 2 hr at 30 °C; mean K + Na + ratio was 3.7 ± 0.5. Tissue slices from Group 2 livers (72 hr preservation), and livers pretreated with CPZ-MP (Group 3) or pretreated with 2-DOC (Group 4) did not significantly reaccumulate K + at 30 °C; mean K + Na + ratio was 1.7–2.1. Only slices prepared from liver pretreated with both CPZ-MP and 2-DOC reaccumulated K + ; mean K + Na + ratio was 4.6 ± 1.2. These findings suggest that the combination of membrane stabilization (CPZ-MP) and stimulated ATP synthesis induced by adding 2-DOC and adenosine to the perfusate is necessary to improve liver preservation.