Ischemic Preconditioning and Intermittent Clamping Increase the Tolerance of Fatty Liver to Hepatic Ischemia-Reperfusion Injury in the Rat

Abstract Introduction Liver ischemia-reperfusion (I/R) injury is a well-known cause of morbidity and mortality following liver surgery and transplantation. Hepatic steatosis increases the extent of cellular injury incurred during I/R injury. We sought to identify measures that reduced the untoward sequelae of liver I/R injury. Methods Male Zucker rats were subjected to 75 minutes of 70% hepatic ischemia, and 3 hours of reperfusion. The ischemic periods were based on the following protocols: continuous clamping (CC) for 75 minutes; intermittent clamping (IC) with five cycles of 15 minutes clamp on and 5 minutes clamp off; or ischemic preconditioning (IP) with 10 minutes clamp on, 15 minutes off, and 60 minutes on ( n = 7 in each group). Warm I/R injury was evaluated using serum levels of aspartate aminotransferase (AST), serum interleukin (IL)-6, as well as hematoxylin and eosin staining. Results Hepatocellular injury was significantly reduced with IP or IC compared with CC (AST: 3285 ± 122.3 and 2875 ± 285.4 compared with 5436.3 ± −984.7 units/L, respectively; P < .01). Serum IL-6 level was also significantly reduced with IP and IC compared with CC (70 ± 8.8 and 76 ± 6.2 compared with 147 ± 8.5 ng/l, respectively ( p < .01). Histological analysis also revealed that IC and IP provided significant protection compared with the CC group. Conclusion IC and IP increased the tolerance of a fatty liver to hepatic I/R injury.