Increasing cycles of intermittent ischemia can effectively maintain liver function during the acute phase of ischemia reperfusion injury by promotion of bile flow and reduction in bile salt toxicity.

Abstract

BACKGROUND/AIMS: Intermittent ischemia (INT) can improve liver function following inflow occlusion. The aim was to test whether the number of cycles of INT can be increased without impairing liver function. METHODS: Liver function in the acute phase of ischemia reperfusion injury was assessed by measuring bile flow in rat livers. Phospholipid and bile salts in bile, liver marker enzymes in blood, and liver histology were measured. Aged livers were compared with young livers. RESULTS: Clamping for 45 min reduced postperfusion bile flow to 13% of the initial value compared with 88 +/- 5% for control livers (means +/- SEM, n = 5-8), and substantially reduced the phospholipid:bile salt ratio in bile. Application of 3, 4, 5 and 6 cycles of INT (15 min) restored bile flow to 70 +/- 11, 61 +/- 4, 48 +/- 2 and 35 +/- 3% (p < 0.01) of the initial value, respectively, and restored the phospholipid:bile salt ratio. Multiple cycles of INT were less effective in aged rats. CONCLUSION: Several cycles of INT, through promotion of bile flow recovery and reduction in the cytotoxic actions of bile salts, may provide an effective clinical strategy for increasing clamping time in liver resections.