EFFECTS OF ISCHEMIA AND REPERFUSION ON LIVER-REGENERATION IN RATS

Objective: To assess the effects of oxygen free radicals on liver rege neration 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 laparotom y 122 rats had ischaemia induced by clamping of the portal vein and he patic artery, and 93 rats had manipulation of the vessels only. They w ere then allowed to recover before 80% hepatectomy was done. Absolute controls (n = 16) did not have a laparotomy. Mortality was recorded, a nd surviving rats were killed one, three, five, and seven days after o peration. A further 10 rats had 80% hepatectomies and then underwent a 10 minute period of ischaemia 24 hours later. These animals were kill ed after three days. In yet more experiments 38 rats underwent 80% hep atectomies and were then divided into four groups: 8 were given allopu rinol 50 mg/kg/day starting three days before operation; 8 were given superoxide dismutase 4.16 mg/kg intraperitoneally 30 minutes before in duction of ischaemia; 12 were given verapamil 0.1 mg/kg 30 minutes bef ore induction of ischaemia; and 10 were given saline (controls). Main outcome measures: Incorporation of tritiated thymidine into DNA, diffe rences in liver weights, and lipid peroxide concentrations. Results: 4 3 rats died after ischaemia/reperfusion and 19 after hepatectomy alone . Ischaemia/reperfusion caused a significant reduction in the incorpor ation 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 wer e associated with high lipid peroxide concentrations at three days. Al lopurinol (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/ r eperfusion on liver weights or lipid peroxide concentrations three day s after hepatectomy. Conclusion: A 10 minute period of ischaemia follo wed by reperfusion temporarily reduces liver regeneration after 80% he patectomy in rats.