EFFECTS OF ISCHEMIA AND REPERFUSION ON LIVER-REGENERATION IN RATS

Objective: To assess the effects of oxygen free radicals on liver regeneration in rats after 80% hepatectomy. Design: Open laboratory study. Setting: Institute of Biomedical Sciences, University of Milan, Italy. Material. Female Sprague-Dawley rats. Interventions: After laparotomy 122 rats had ischaemia induced by clamping of the portal vein and hepatic artery, and 93 rats had manipulation of the vessels only. They were then allowed to recover before 80% hepatectomy was done. Absolute controls (n = 16) did not have a laparotomy. Mortality was recorded, and surviving rats were killed one, three, five, and seven days after operation. A further 10 rats had 80% hepatectomies and then underwent a 10 minute period of ischaemia 24 hours later. These animals were killed after three days. In yet more experiments 38 rats underwent 80% hepatectomies and were then divided into four groups: 8 were given allopurinol 50 mg/kg/day starting three days before operation; 8 were given superoxide dismutase 4.16 mg/kg intraperitoneally 30 minutes before induction of ischaemia; 12 were given verapamil 0.1 mg/kg 30 minutes before induction of ischaemia; and 10 were given saline (controls). Main outcome measures: Incorporation of tritiated thymidine into DNA, differences in liver weights, and lipid peroxide concentrations. Results: 43 rats died after ischaemia/reperfusion and 19 after hepatectomy alone. Ischaemia/reperfusion caused a significant reduction in the incorporation of tritiated thymidine into DNA 24 hours after hepatectomy (p < 0.01), and significant inhibition of recovery of liver weight three (p < 0.01) and five (p < 0.05) days after hepatectomy. These effects were associated with high lipid peroxide concentrations at three days. Allopurinol (p < 0.01, p < 0.05), superoxide dismutase (p < 0.01, p < 0.01) and verapamil (p < 0.01, N.S.) reduced the effects of ischaemia/ reperfusion on liver weights or lipid peroxide concentrations three days after hepatectomy. Conclusion: A 10 minute period of ischaemia followed by reperfusion temporarily reduces liver regeneration after 80% hepatectomy in rats.