The effect of various methods of inflow occlusion techniques in a rat liver resection on the extent of the liver injury and liver regeneration

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Introduction : Both intermittent clamping (IC) and ischemic preconditioning (I/Pr) have been shown to protect the liver against ischemia/reperfusion (I/R) injury. While IC cycles consisting of 15 to 20 minutes' clamping alternating with 5 minutes' reperfusion are used empirically during liver resection, the optimal IC cycle, i.e., the optimal lengths of clamping and reperfusion, are not yet established. Aim : To examine the hypothesis that IC with shorter clamping/reperfusion cycles are desirable, and to compare various IC and I/Pr protocols in terms of their efficacy in reducing I/R injury. Methods Male Wistar rats (250-270g) were randomly assigned into five groups ; 60 minutes' continuous ischemia (60*1 min, n=12), 4 cycles of 15 minutes' ischemia/5 minutes' reperfusion (15*4 min, n=12), 6 cycles of 10 minutes' ischemia/3.3 minutes' reperfusion (10*6 min, n=10), 12 cycles of 5 minutes' ischemia/1.7 minutes' reperfusion (5*12 min, n=9), preconditioning (10 minutes' ischemia and 10 min … More utes' reperfusion) prior to 60 minutes' ischemia (I/Pr, n=9). The total ischemic time was fixed at 60 minutes in all the groups, and the ratio of the ischemic time to reperfusion time was fixed at 3:1 in each of the IC groups. After 3 hours of reperfusion, the severity of liver injury was assessed by measuring the serum ALT levels, bile flow, H&E staining of liver specimens, TUNEL staining and DNA laddering as specific markers of apoptosis, and the tissue gluthatione (GSH) content (IC groups only). Results : The data were presented as mean± SEM in the following order of experimental groups, respectively : 60*1 min, 15*12 min, 10*6 min, 5*12 min, and I/Pr groups. The serum ALT levels (IU/L) were 4227±482, 3202±400, 2044±191, 761±108, and 6981±691 (p<0.001). Bile flow (μg/ml) were 230±70, 620±60, 760±80, 980±70, and 190±50 (p<0.001). H&E staining were : large confluent areas of tissue destruction, mild parenchymal injury including occasional cellular swelling and cytoplasmic vacuolization, minimal alterations, minimal alterations, and mild parenchymal injury. The percentages of TUNEL-positive hepatocytes (%) were : >50, 20-25, <3 , <3 , and 20-25. The tissue GSH content (%) decreased from baseline value to 59.7±0.8, 60.5±2.9, 73.8±2.8, and 81.4±3.4 (p<0.001, I/Pr group was not assessed). Conclusion : In terms of protection against warm I/R injury, IC with shorter cycles of ischemia and reperfusion appears to be more effective than that with longer cycles. The protective effect of I/Pr was not uniform in the present study. IC may be a more robust strategy than I/Pr, regardless of the lengths of the cycles of clamping and reperfusion or the parameters evaluated. Less