Protection of the Liver by Ischemic Preconditioning: A Review of Mechanisms and Clinical Applications

Koti, Rahul; Seifalian, Alexander M.; Davidson, Brian R

doi:10.1159/000072064

Cited by 115 publications

(90 citation statements)

References 73 publications

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“…NHBD programs have been used successfully in kidney transplantation, and were able to increase donor pool of kidneys by 40%. In the field of liver transplantation the use of livers from NHBD shows a less favorable clinical results, because of the limited hepatic tolerance against warm ischemic damage compared with kidneys [28][29][30] . Although several clinical and experimental studies have shown that liver can compensate 60 min of WIT during liver resection [31,32] , in transplantation settings, there were few studies about limit of the period of warm ischemia before transplantation.…”

Section: Discussionmentioning

confidence: 99%

Safe time to warm ischemia and posttransplant survival of liver graft from non-heart-beating donors

He¹

2004

WJG

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AIM:To explore the dynamical changes of histology, histochemistry, energy metabolism, liver microcirculation, liver function and posttransplant survival of liver graft in rats under different warm ischemia times (WIT) and predict the maximum limitation of liver graft to warm ischemia. METHODS:According to WIT, the rats were randomized into 7 groups, with WIT of 0, 10, 15, 20, 30, 45, 60 min, respectively. The recovery changes of above-mentioned indices were observed or measured after liver transplantation. The graft survival and postoperative complications in each subgroup were analyzed. RESULTS:Liver graft injury was reversible and gradually resumed normal structure and function after reperfusion when WIT was less than 30 min. In terms of graft survival, there was no significant difference between subgroups within 30 min WIT. When WIT was prolonged to 45 min, the recipients' long-term survival was severely insulted, and both function and histological structure of liver graft developed irreversible damage when WIT was prolonged to 60 min. CONCLUSION:The present study indicates that rat liver graft can be safely subjected to warm ischemia within 30 min. The levels of ATP, energy charge, activities of glycogen, enzyme-histochemistry of liver graft and its recovery potency after reperfusion may serve as the important criteria to evaluate the quality of liver graft.

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Section: Discussionmentioning

confidence: 99%

Safe time to warm ischemia and posttransplant survival of liver graft from non-heart-beating donors

He¹

2004

WJG

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“…This has motivated a search for new approaches to reduce ischemic injury, among which ischemic preconditioning (IPC) constitutes a prominent promising strategy. This endogenous adaptive mechanism of protection against a sustained ischemic insult is afforded by exposure to an initial, brief ischemic stimulus followed by a period of reperfusion or by the administration of chemical agents, which is known as pharmacological preconditioning (PC) [2][3][4]. In livers, PC can reduce the release of transaminases, increase the survival of rodents after liver transplantation, and even improve human hepatic functions after major liver surgery in patients subjected to 30 min of ischemia [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…In livers, PC can reduce the release of transaminases, increase the survival of rodents after liver transplantation, and even improve human hepatic functions after major liver surgery in patients subjected to 30 min of ischemia [5][6][7][8]. Furthermore, IPC decreases liver injury after both warm and cold I/R [2,4,9,10]. Several mechanisms have been proposed for protection by IPC, including activation of adenosine receptors [11][12][13][14], increased nitric oxide production [15], activation of protein kinase C [16], up-regulation of heat shock proteins, and increased antioxidant capacity [17,18].…”

Section: Introductionmentioning

confidence: 99%

Adenosine receptors: regulatory players in the preservation of mitochondrial function induced by ischemic preconditioning of rat liver

Duarte

Amorim

Varela

et al. 2016

Purinergic Signalling

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Although adenosine A 1 receptors (A1R) have been associated to ischemic preconditioning (IPC), direct evidence for their ability to preserve mitochondrial function upon hepatic preconditioning is still missing and could represent a novel strategy to boost the quality of liver transplants. We tested if the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) prevented IPC in the liver and if the A1R agonist 2-chloro-N 6 -cyclopentyladenosine (CCPA) might afford a pharmacological preconditioning. Livers underwent a 120 min of 70% warm ischemia and 16 h of reperfusion (I/R), and the IPC group underwent a 5-min ischemic episode followed by a 10-min period of reperfusion before I/R. DPCPX or CCPA was administered intraperitoneally 2 h before IPC or I/R. The control of mitochondrial function emerged as the central element affected by IPC and controlled by endogenous A1R activation. Thus, livers from IPC-or CCPA-treated rats displayed an improved oxidative phosphorylation with higher state 3 respiratory rate, higher respiratory control ratio, increased ATP content, and decreased lag phase. IPC and CCPA also prevented the I/Rinduced susceptibility to calcium-induced mitochondrial permeability transition, the rate of reactive oxygen species (ROS) generation, and the decreased mitochondrial content of phospho-Ser 9 GSK-3β. DPCPX abrogated these effects of IPC. These implicate the control of GSK-3β activity by Aktmediated Ser 9 -GSK-3β phosphorylation preserving the efficiency of oxidative phosphorylation and ROS-mediated cell death in the ability of A1R activation to mimic IPC in the liver. In conclusion, the parallel between IPC and A1R-mediated preconditioning also paves the way to consider a putative therapeutic use of the later in liver transplants.

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“…Ischemic pre-conditioning (IPC) refers to brief episodes of ischemia followed by prolonged ischemia and reperfusion and has been shown to protect organs against ischemia/reperfusion injury [1] . Although, it was studied extensively in a variety of organs, including skeletal muscle, brain, spinal cord, kidney, intestine, heart and liver, the mechanisms of its protective effects remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats

Yuan

Ma²,

Gong³

et al. 2005

WJG

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AIM:To investigate effects of ischemic pre-conditioning on the liver endogenous oxidant-antioxidant system during ischemia/reperfusion injury. METHODS:Twenty-four male Sprague-Dawley rats were randomly divided into sham-operated (Sham), ischemia/ reperfusion (I/R), ischemic pre-conditioning plus ischemia/ reperfusion (IPC) groups. Serum ALT, AST and hyaluronic acid levels were assayed and pathologic alterations observed. Liver malondialdehyde (MDA) contents, endogenous antioxidant enzymes, superoxidase dismutase (SOD), catalase (CAT), gultathionine peroxidase (GSH-Px) activities, neutrophils accumulation marker, myeloperoxidase (MPO) activities were measured respectively. RESULTS:Compared with I/R group, sinusoidal endothelial cells as well as hepatocytes damages, as assessed biochemically and histochemically, were improved significantly in IPC group; neutrophils infiltration was also markedly reduced. In IPC group, liver peroxidation, as measured by MDA contents, was significantly decreased when compared with I/R group; endogenous antioxidant enzymes, SOD, CAT and GSH-Px activities were markedly higher than that in I/R group. CONCLUSION:Ischemic pre-conditioning exerts protective effects on both hepatic sinusoidal endothelial cells and hepatocytes during liver I/R injury. Its mechanisms may involve dimunition of neutrophils infiltration and modulation of the imbalance of endogenous oxidant-antioxidant system in the organism.

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Protection of the Liver by Ischemic Preconditioning: A Review of Mechanisms and Clinical Applications

Cited by 115 publications

References 73 publications

Safe time to warm ischemia and posttransplant survival of liver graft from non-heart-beating donors

Safe time to warm ischemia and posttransplant survival of liver graft from non-heart-beating donors

Adenosine receptors: regulatory players in the preservation of mitochondrial function induced by ischemic preconditioning of rat liver

Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats

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