Effect of remote ischemic preconditioning in the expression of IL-6 and IL-10 in a rat model of liver ischemia-reperfusion injury

Filho, Marco Antonio Correa Guimarães; Cortez, Erika; Garcia-Souza, Érica Patrícia; Soares, Vivian de Melo; Moura, Aníbal Sanchez; Carvalho, Luiz Roberto; Maya, Maria Cristina de Araujo; Pitombo, Marcos Bettini

doi:10.1590/s0102-865020150070000002

Cited by 19 publications

(23 citation statements)

References 30 publications

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Section: Discussionmentioning

confidence: 91%

“…RIPC has been shown by our own group and others to ameliorate hepatic IR injury in small animal models 12,13,14,15 . It has also been translated into clinical benefit in patients undergoing both cardiac surgery 16 The aims of this study was to perform a prospective randomized controlled feasibility study to address these issues and to obtain preliminary data on which to design a further prospective trial to determine efficacy and cost effectiveness.…”

mentioning

confidence: 91%

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Remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial): a pilot randomized controlled feasibility study

Robertson

Goswami

Wright

et al. 2017

HPB

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Abstract:Ischaemia Reperfusion (IR) injury is a major cause of post-operative morbidity, mortality and graft loss following Orthotopic Liver Trasnplantation (OLT). There is no current accepted treatment for IR injury. The recent drive to implant more marginal grafts, which are more susceptible to IR injury makes this clinical problem a key research goal. Remote Ischaemic Preconditioning (RIPC) has been shown to ameliorate hepatic IR injury in small animal models. Whether recipient RIPC can reduce IR injury in human liver transplant recipients has not previously been investigated. Methods:Forty patients with end stage liver disease undergoing liver transplantation were randomized to RIPC or a sham control group. RIPC was induced through three 5 minute cycles of alternate ischaemia and reperfusion using an orthopaedic tourniquet to the left lower limb under general anaesthesia prior to commencement of the abdominal procedure. The aim of the study was to determine the safety and feasibility of limb RIPC in patients with end stage cirrhosis. Data on clinical outcomes was collected prospectively (minimum 3 month follow up) and the function of the graft was also evaluated. Plasma cytokine levels were measured at baseline, 2 hours post reperfusion and at 24 hours post-operatively. Results:45 of 51 patients approached (88%) were willing to enroll in the study. 5 patients were then excluded and 40 patients were randomized of which 20 underwent RIPC.RIPC was able to be performed in all patients randomized to the RIPC group. There was no evidence of localized complications following RIPC. One patient died in the control group and 1 further graft was lost in the control group due to a non-IR related 3 issue. Median AST levels on the third post-operative day showed a slightly higher trend in the RIPC group than in the control group (221iU vs 149iU, p=1.00) but this was not statistically significant. Conclusions:RIPC is acceptable and can be carried out safely in patients with advanced liver disease. This pilot feasibility study has not demonstrated evidence of a reduction in IR injury or clinical benefit. A longer follow up, a larger study or an altered preconditioning protocol may be required. 4Liver transplantation is the treatment of choice for both acute and chronic end stage liver disease. As outcomes following transplantation have improved, the indications for liver transplantation have been widened and a shortage of suitable organ donors has developed. This has resulted in an increased use of grafts from marginal donors such as the elderly and those with a fatty liver from obesity (extended criteria donors) and especially the use of grafts from donors following cardiac death (DCD). The use of liver DCD grafts in the UK has increased from 6.9% in 2005 1 to 19.1% of grafts implanted in 2013 2 .Ischaemia Reperfusion (IR) injury is the damage that happens to an organ when its blood supply is interrupted and reconstituted. It is a major cause of morbidity and mortality following liver transplantation and is believed to acc...

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Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 91%

Remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial): a pilot randomized controlled feasibility study

Robertson

Goswami

Wright

et al. 2017

HPB

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“… have demonstrated that remote IPC on the limbs results in favourable changes in mitochondrial oxygenation, serum bicarbonate and hepatic venous nitric oxide (NO), NO protects against MPT‐dependent apoptosis through the cGMP‐dependent kinase signalling pathway . One study has executed IPC in the right hind limbs of rats with six cycles of pre‐condition clamping and reperfusion and has found that the attenuated liver necrosis is mediated by the up‐regulation of interleukin(IL)‐6 . In addition to remote IPC on limbs, intestinal IPC has also eliminated hepatic IR‐induced injury by decreasing inflammatory cytokines and enhancing Bcl‐2 expression .…”

Section: Ipc For Attenuating Hepatic Ir Injurymentioning

confidence: 99%

Pre‐conditions for eliminating mitochondrial dysfunction and maintaining liver function after hepatic ischaemia reperfusion

Hu¹

2017

J Cellular Molecular Medi

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The liver, the largest organ with multiple synthesis and secretion functions in mammals, consists of hepatocytes and Kupffer, stem, endothelial, stellate and other parenchymal cells. Because of early and extensive contact with the external environment, hepatic ischaemia reperfusion (IR) may result in mitochondrial dysfunction, autophagy and apoptosis of cells and tissues under various pathological conditions. Because the liver requires a high oxygen supply to maintain normal detoxification and synthesis functions, it is extremely susceptible to ischaemia and subsequent reperfusion with blood. Consequently, hepatic IR leads to acute or chronic liver failure and significantly increases the total rate of morbidity and mortality through multiple regulatory mechanisms. An increasing number of studies indicate that mitochondrial structure and function are impaired after hepatic IR, but that the health of liver tissues or liver grafts can be effectively rescued by attenuation of mitochondrial dysfunction. In this review, we mainly focus on the subsequent therapeutic interventions related to the conservation of mitochondrial function involved in mitigating hepatic IR injury and the potential mechanisms of protection. Because mitochondria are abundant in liver tissue, clarification of the regulatory mechanisms between mitochondrial dysfunction and hepatic IR should shed light on clinical therapies for alleviating hepatic IR‐induced injury.

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“…RIPC induced HO-1 expression in several organs, but not in the skin. Interestingly, HO-1 can also promote regeneration in a paracrine fashion via its versatile effector molecules biliverdin/bilirubin, CO, and ferritin [20,50,51,52,53,54], which are increased following (R)IPC [55,56,57,58]. Moreover, RIPC-mediated protection can act via various alternative signaling pathways, including humoral, neuronal, and systemic mechanisms [22,59].…”

Section: Resultsmentioning

confidence: 99%

Effects of Remote Ischemic Preconditioning on Heme Oxygenase-1 Expression and Cutaneous Wound Repair

Cremers

Wever

Wong

et al. 2017

IJMS

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Skin wounds may lead to scar formation and impaired functionality. Remote ischemic preconditioning (RIPC) can induce the anti-inflammatory enzyme heme oxygenase-1 (HO-1) and protect against tissue injury. We aim to improve cutaneous wound repair by RIPC treatment via induction of HO-1. RIPC was applied to HO-1-luc transgenic mice and HO-1 promoter activity and mRNA expression in skin and several other organs were determined in real-time. In parallel, RIPC was applied directly or 24h prior to excisional wounding in mice to investigate the early and late protective effects of RIPC on cutaneous wound repair, respectively. HO-1 promoter activity was significantly induced on the dorsal side and locally in the kidneys following RIPC treatment. Next, we investigated the origin of this RIPC-induced HO-1 promoter activity and demonstrated increased mRNA in the ligated muscle, heart and kidneys, but not in the skin. RIPC did not change HO-1 mRNA and protein levels in the wound 7 days after cutaneous injury. Both early and late RIPC did not accelerate wound closure nor affect collagen deposition. RIPC induces HO-1 expression in several organs, but not the skin, and did not improve excisional wound repair, suggesting that the skin is insensitive to RIPC-mediated protection.

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Effect of remote ischemic preconditioning in the expression of IL-6 and IL-10 in a rat model of liver ischemia-reperfusion injury

Cited by 19 publications

References 30 publications

Remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial): a pilot randomized controlled feasibility study

Remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial): a pilot randomized controlled feasibility study

Pre‐conditions for eliminating mitochondrial dysfunction and maintaining liver function after hepatic ischaemia reperfusion

Effects of Remote Ischemic Preconditioning on Heme Oxygenase-1 Expression and Cutaneous Wound Repair

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