Ischemic Preconditioning Increases the Tolerance of Fatty Liver to Hepatic Ischemia-Reperfusion Injury in the Rat (original) (raw)
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Journal of investigative surgery : the official journal of the Academy of Surgical Research, 2017
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. 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. 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...
BioMed research international, 2013
The impact of hepatic steatosis on outcome following hepatic ischemia-reperfusion injury (IRI) remains controversial with conflicting clinical results. A number of experimental studies have been published examining the relationship between hepatic steatosis and IRI. This systematic review evaluates these experimental studies. An electronic search of the Medline and Embase databases (January 1946 to June 2012) was performed to identify studies that reported relevant outcomes in animal models of hepatic steatosis subjected to IRI. A total of 1314 articles were identified, of which 33 met the predefined criteria and were included in the study. There was large variation in the type of animal model, duration, and type of IRI and reporting of histological findings. Increased macrovesicular steatosis (>30%) was associated with increased histological damage, liver function derangement, and reduced survival. Increased duration of warm or cold ischemia had a negative impact on all outcomes...
Hellenic Journal of Surgery, 2019
Introduction: Fatty liver disease (FLD) is becoming increasingly common. Ischemia-reperfusion injury (IRI) is the main pathogenic factor determining morbidity and mortality after major hepatic surgery. This experimental study investigated changes in the levels of interleukin 6 (IL6), tumor necrosis factor α (TNFα), nitric oxide (NO), glutathione (GSH) and lactic acid (LA) in hepatic tissue, in normal rats and rats with severe hepatic steatosis, after 30-minute hepatic ischemia and reperfusion. The aim was to evaluate the ability of the severely steatotic liver to sustain ischemia. Method: The study was conducted on 96 male Wistar rats aged 12-14 weeks, in 48 of which severe hepatic steatosis was induced by administration of a choline-free diet for 12-14 weeks. The other 48 rats received standard laboratory diet for the same period. The effect of 30-minute hepatic ischemia and reperfusion was examined in 24 steatotic and 24 lean livers, which were subjected to hepatic ischemia-reperfusion injury. After 6 and 24 hours of reperfusion, the levels of IL6, TNFα, NO, LA and GSH in the liver tissue of all the rats were measured. The serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) were measured to determine the severity of hepatic injury, and the survival of the rats after surgery was assessed. Results: Rats with steatotic livers subjected to 30-minute hepatic ischemia and reperfusion showed significantly higher liver values of TNFα and LA and significantly lower liver values of IL6, GSH and NO than lean rats. The serum levels of AST and ALT were higher in rats with severely steatotic livers than in those with lean livers, after 30-minute hepatic ischemia and reperfusion, and no rat with a steatotic liver survived surgery. Conclusion: Rats with steatotic livers undergoing 30-minute ischemia and reperfusion show significant elevation of TNFα and LA and reduction in IL6, GSH and NO in liver tissue, with poor survival after surgery, compared to non-steatotic rats. These findings suggest that steatotic livers are more susceptible to ischemia-reperfusion injury than lean livers.
Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning
American journal of physiology. Gastrointestinal and liver physiology, 2003
Ischemia-reperfusion injury is, at least in part, responsible for the morbidity associated with liver surgery under total vascular exclusion or after liver transplantation. The pathophysiology of hepatic ischemia-reperfusion includes a number of mechanisms that contribute to various degrees in the overall injury. Some of the topics discussed in this review include cellular mechanisms of injury, formation of pro- and anti-inflammatory mediators, expression of adhesion molecules, and the role of oxidant stress during the inflammatory response. Furthermore, the roles of nitric oxide in preventing microcirculatory disturbances and as a substrate for peroxynitrite formation are reviewed. In addition, emerging mechanisms of protection by ischemic preconditioning are discussed. On the basis of current knowledge, preconditioning or pharmacological interventions that mimic these effects have the greatest potential to improve clinical outcome in liver surgery involving ischemic stress and rep...
Effects of Ischemic Liver Preconditioning on Hepatic Ischemia/Reperfusion Injury in the Rat
Transplantation Proceedings, 2007
To minimize bleeding during major liver resections or liver transplantation, surgical measures have been adopted that induce ischemia-reperfusion injury (I/R) which may significantly contribute to morbidity and mortality of partial liver resections. Several methods have sought to minimize I/R hepatic lesions. The present project assessed the protective role of ischemic preconditioning (IPC) in rat livers. The IPC was accomplished by
The Open Transplantation Journal, 2013
Background: The impact of hepatic steatosis on bioenergetics following hepatic ischemia-reperfusion injury (IRI) remains controversial and is associated with variable reports on its outcome. Large numbers of studies have been published examining the relationship between hepatic steatosis and cellular bioenergetics following hepatic IRI. This systematic review evaluates these studies. Methods: An electronic search of the Medline and Embase databases (January 1946 to June 2012) was performed to select studies that reported relevant outcomes in animal models or patients with hepatic steatosis subjected to IRI. Results: A total of 489 articles were identified, of which 63 animal studies met the predefined criteria and were included in the study. There was large variation in the type of animal model, duration and type of IRI utilized and histological description of hepatic steatosis. Bioenergetic impairments appear to increase the susceptibility of steatotic livers to IRI. The most common impairment was decreased adenosine triphosphate recovery with increased oxidative stress following IRI. Impaired mitochondrial function play a key role in the susceptibility of steatotic livers to IRI. Conclusions: Animals with >30% hepatic steatosis have been shown to have poor outcome following IRI. Despite limitations of different experimental models and inconsistency in histological description, impaired mitochondrial function and bioenergetics appear to be important mediators in the decreased tolerance of steatotic livers to IRI. Future studies need to be consistent and clinically relevant to further improve our understanding of this issue.
Acta cirurgica brasileira, 2018
It is well known that during hepatic operative procedures, it is often critical that the irrigation is interrupted to avoid possible bleeding, blood transfusions, variable intensities, and their short and long-term consequences. It was believed in the past that the flow interruption should not exceed 20 minutes, which limited the use of this maneuver. However, it has been postulated that ischemia could be maintained for more than 60 minutes in healthy livers. The present paper review includes: 1) A brief introduction to justify the rationale of the review design; 2) Aspects of the pathophysiology of the three stages of the liver ischemia-reperfusion injury; 3) The innate and acquired immunity; 4) Oxidative stress; 5) Apoptosis and autophagy, Some essential biomarkers (Tumor Necrosis Factor-α, nitric oxide, metalloproteinases); and, finally; 6) Preventive ("cheating") strategies, non-pharmacological and pharmacological options to treat the liver IR injury.
AJP: Gastrointestinal and Liver Physiology, 2006
Steatosis is a major risk factor for complications after liver surgery. Since neutrophil cytotoxicity is critical for ischemia-reperfusion injury in normal livers, the aim of the present study was to evaluate whether an exaggerated inflammatory response could cause the increased injury in steatotic livers. In C57Bl/6 mice, 60 min of warm hepatic ischemia triggered a gradual increase in hepatic neutrophil accumulation during reperfusion with peak levels of 100-fold over baseline at 12 h of reperfusion. Neutrophil extravasation and a specific neutrophil-induced oxidant stress (immunostaining for hypochlorous acid-modified epitopes) started at 6 h of reperfusion and peaked at 12–24 h. Ob/ob mice, which had a severe macrovesicular steatosis, suffered significantly higher injury (alanine transaminase activity: 18,000 ± 2,100 U/l; 65% necrosis) compared with lean littermates (alanine transaminase activity: 4,900 ± 720 U/l; 24% necrosis) at 6 h of reperfusion. However, 62% fewer neutrophil...
Journal of Clinical Medicine
Liver Ischaemia Reperfusion (IR) injury is a major cause of post-operative liver dysfunction, morbidity and mortality following liver resection surgery and transplantation. There are no proven therapies for IR injury in clinical practice and new approaches are required. Ischaemic Preconditioning (IPC) can be applied in both a direct and remote fashion and has been shown to ameliorate IR injury in small animal models. Its translation into clinical practice has been difficult, primarily by a lack of knowledge regarding the dominant protective mechanisms that it employs. A review of all current studies would suggest that IPC/RIPC relies on creating a small tissue injury resulting in the release of adenosine and L-arginine which act through the Adenosine receptors and the haem-oxygenase and endothelial nitric oxide synthase systems to reduce hepatocyte necrosis and improve the hepatic microcirculation post reperfusion. The next key step is to determine how long the stimulus requires to precondition humans to allow sufficient injury to occur to release the potential mediators. This would open the door to a new therapeutic chapter in this field.