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

J Invest Surg. 2018 Oct;31(5):366-377. doi: 10.1080/08941939.2017.1334844. Epub 2017 Jun 23.


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.

Keywords: extensive hepatectomy; fatty liver disease; intermittent ischemic preconditioning; ischemia-reperfusion injury; simple ischemic preconditioning; steatotic liver.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Fatty Liver / mortality
  • Fatty Liver / surgery*
  • Hepatectomy / adverse effects*
  • Hepatectomy / methods
  • Humans
  • Ischemic Preconditioning / methods*
  • Liver / blood supply*
  • Liver Function Tests
  • Male
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / etiology
  • Reperfusion Injury / mortality
  • Reperfusion Injury / prevention & control*
  • Survival Rate
  • Treatment Outcome