How much ischemia can the severely steatotic rat liver tolerate?

Aim: Steatotic liver is more susceptible to ischemia-reperfusion injury than is lean liver. Our aim was to investigate the ability of the severely steatotic rat liver to sustain ischemia. Materials and Methods: One hundred male Wistar rats aged 12-14 weeks were included. Fifty rats were given regular diet, while the rest were given a choline-free diet for 12-14 weeks to develop severe liver steatosis. Each group was divided into the following five subgroups: Shamoperated, and 5, 10, 15 and 20 minutes of continuous vascular inflow occlusion. Serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase levels were measured at 24 hours postoperatively and the animals were surveilled for 30 days. Results: Serum transaminase levels increased as the duration of ischemia increased in lean livers (p<0.0001), without a significant impact on animal survival. Similarly, serum transaminase levels increased as the duration of ischemia increased in severely steatotic livers (p<0.0001), reaching a plateau after 15 minutes of liver ischemia. Survival was significantly affected after the same cut-off point in rats with steatotic liver (p<0.0001). Serum transaminase levels were greater in severely rats with steatotic liver than in rats with lean liver, when they were adjusted for the duration of liver ischemia. Moreover, survival was reduced when serum transaminase levels surpassed the threshold of 2,000 IU/l (p<0.0001). Conclusion: Severely steatotic rat liver can safely tolerate up to 10 minutes of continuous ischemia, with survival being affected after 15 minutes or more. On the other hand, lean rat liver can safely tolerate even 20 minutes of continuous ischemia. © 2018 Institute of Electrical and Electronics Engineers Inc. All rights reserved

Histopathological changes and onset of severe hepatic steatosis in rats fed a choline-free diet

Hepatic steatosis significantly increases morbidity and mortality associated with major liver surgery. Several rodent models of hepatic steatosis have been previously reported, which aimed to investigate the effect of various pharmaceutical agents and interventional procedures on the pathophysiology of steatotic liver. The aim of the present study was to investigate the time frame of severe hepatic steatosis in rats after they were fed a choline-free diet and any associated histopathological changes. The duration of feeding with a choline-free diet required to develop severe hepatic steatosis was investigated in Wistar rats. The severity of hepatic steatosis in liver specimens was evaluated at 8, 10, 12 and 14 weeks following the onset of the choline-free diet. Comparisons were made with rats receiving standardized laboratory food. Feeding rats for 12-13 weeks with a choline-free diet led to 66% fatty liver infiltration, which exceeded 68% after 14 weeks. Prior to 8 weeks, the fatty infiltration reached 43%, with a gradual increase revealing a stronger rate from 8-12 weeks and a gradual decline after 14 weeks. At 12-13 weeks the fatty infiltration was considered representative of severe hepatic steatosis. Macrovesicular fatty infiltration revealed a significant increase at a steady rate between 8 and 14 weeks, with evidence of the onset of lobular inflammation and steatohepatitis after 14 weeks of feeding with the choline-free diet. Microvesicular fatty infiltration demonstrated a lower growth rate between 8 and 12 weeks while maintaining a steady rate between 12 and 14 weeks. Mixed fatty infiltration maintained its steady rate of hepatic parenchyma from 8.8-9.5%. Rats fed with the standard laboratory diet did not demonstrate fatty infiltration >4.5%, so they did not develop hepatic steatosis. Developing an ideal model of hepatic steatosis is a particular challenge. The findings of the present study indicate that severe hepatic steatosis in rodents may lead to the development of steatohepatitis after feeding with a choline-free diet for at least 14 weeks. This model is of particular interest in experimental liver surgery and associated surgical maneuvers, and is easily reproducible. © 2018, Spandidos Publications. All rights reserved

Intermittent Ischemic Preconditioning Protects Against Hepatic Ischemia-Reperfusion Injury and Extensive Hepatectomy in Steatotic Rat Liver

Background: Hepatic steatosis causes severe liver damage and has deleterious effects when associated with ischemia-reperfusion mechanisms. Ischemic preconditioning (IPC) protects lean liver against prolonged ischemia by improving micro-circulation and reducing lipid peroxidation. We investigated the effect of intermittent IPC on liver ischemia-reperfusion injury (IRI) and extensive hepatectomy in severe hepatic steatosis. Methods: Severe hepatic steatosis was performed by 12–14 weeks of choline-free diet in 108 Wistar rats. We induced 30-minute ischemia-reperfusion manipulations and extensive hepatectomy with or without prior IPC in steatotic livers and after 6 and 24 hours of reperfusion blood transaminases, and IL6, TNFα, NO and Lactate in blood and liver tissue were measured. Results: Steatotic rats subjected to hepatic ischemia-reperfusion alone after extensive hepatectomy, showed severe liver damage with significantly increased values of AST, ALT, TNFα and Lactate and significantly reduced IL6 and NO, while no one rat survived for more than 29 hours. On the contrary, steatotic rats subjected to intermittent IPC, 24 hours before ischemia-reperfusion, presented increased 30-day survival (67%), lower values of AST, ALT, TNFα and Lactate, and increased IL6 and NO levels. Simple and intermittent IPC manipulations, 1 hour before the IRI and extended hepatectomy, did not prolong survival more than 57 and 98 hours, respectively. Simple IPC, 24 hours before IRI and extended hepatectomy had the lowest possible survival (16.7%).Conclusions: Hepatic steatosis and IRI after major liver surgery largely affect morbidity and mortality. Intermittent IPC, 24 hours before IRI and extensive hepatectomy, presents higher 30-day survival and improved liver function parameters. © 2017, Copyright © 2017 Taylor & Francis Group, LLC