Intermittent clamping is superior to ischemic preconditioning and its effect is more marked with shorter clamping cycles in the rat liver

Abstract

Intermittent clamping (IC) and ischemic preconditioning (PC) reportedly protect the liver against the ischemia/reperfusion (I/R) injury induced by inflow occlusion during hepatectomy. While IC cycles consisting of 15 min of clamping with 5 min of reperfusion are used empirically, the optimal IC cycle has not been established. We compared the effects of various cycles of IC and PC in the rat liver. Rats subjected to 60 min of inflow occlusion were assigned to the following five groups (n = 8 each): 60 min of continuous ischemia; 4 cycles comprising 15 min of ischemia/5 min of reperfusion; 6 cycles comprising 10 min of ischemia/3.3 min of reperfusion; 12 cycles comprising 5 min of ischemia/1.7 min of reperfusion (the time ratio of ischemia to reperfusion in the IC groups was 3:1); and PC (10/10 min of ischemia/reperfusion) prior to 60 min of ischemia. The severity of liver injury was assessed by determining the serum alanine aminotransferase (ALT) level, bile flow, tissue glutathione content, and induction of apoptosis (terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling [TUNEL] staining and DNA laddering), and by histological examination of areas of severe necrosis. All the parameters indicated that liver injury was attenuated in the three IC groups compared with the continuous group; furthermore, this effect became increasingly marked with shorter cycles of IC. PC did not exert a protective effect under the present experimental conditions. Various cycles of IC consistently conferred protection against I/R injury, and IC with shorter cycles of ischemia and reperfusion was more effective. No protective effect of PC was evident. IC is a more robust strategy than the PC protocol for liver protection.