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Ischemic tolerance is a robust internal defense mechanism of all living organisms. The effectiveness of this mechanism has been repeatedly demonstrated in experiments, but a comprehensive review of the clinical applicability of this phenomenon in practice has not yet been published. The results in clinical practice sound ambiguous and unconvincing in comparison with the results of experimental studies. Also, in many localities, the effect of ischemic tolerance was not clinically proven. For the reasons mentioned, the authors analyze the possible causes of the mentioned discrepancies and provide a comprehensive insight into the possible relevant clinical use of this phenomenon in practice for different groups of patients., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Remote ischemic preconditioning (RIPC) exerts a protective role on myocardial ischemia/reperfusion (I/R) injury by the release of various humoral factors. Lactate is a common metabolite in ischemic tissues. Nevertheless, little is known about the role lactate plays in myocardial I/R injury and its underlying mechanism. This investigation revealed that RIPC elevated the level of lactate in blood and myocardium. Furthermore, AZD3965, a selective monocarboxylate transporter 1 inhibitor, and 2-deoxy-d-glucose, a glycolysis inhibitor, mitigated the effects of RIPC-induced elevated lactate in the myocardium and prevented RIPC against myocardial I/R injury. In an in vitro hypoxia/reoxygenation model, lactate markedly mitigated hypoxia/reoxygenation-induced cell damage in H9c2 cells. Further studies suggested that lactate contributed to RIPC, rescuing I/R-induced autophagy deficiency by promoting transcription factor EB (TFEB) translocation to the nucleus through activating the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway without influencing the phosphatidylinositol 3-kinase-Akt pathway, thus reducing cardiomyocyte damage. Interestingly, lactate up-regulated the mRNA and protein expression of connexin 43 (CX43) by facilitating the binding of TFEB to CX43 promoter in the myocardium. Functionally, silencing of TFEB attenuated the protective effect of lactate on cell damage, which was reversed by overexpression of CX43. Further mechanistic studies suggested that lactate facilitated CX43-regulated autophagy via the AMPK-mTOR-TFEB signaling pathway. Collectively, this research demonstrates that RIPC protects against myocardial I/R injury through lactate-mediated myocardial autophagy via the AMPK-mTOR-TFEB-CX43 axis., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: Acute cerebral infarction (ACI) contributes to disability and death accross the globe. Remote ischemic preconditioning (RIPC) reduces cerebral infarct size and improves neurological function in ACI. We conducted this research to reveal the effects of RIPC intervention on serum levels of microRNA-582-5p (miR-582-5p)/high mobility group box-1 protein (HMGB1), inflammation, oxidative stress and neurological function in patients with ACI., Methods: In this study, 158 patients with ACI were prospectively selected and randomized into the control (administered symptomatic medication alone) and the RIPC (underwent RIPC of the limbs based on medication) groups, with their clinical baseline data documented. Serum levels of miR-582-5p, and HMGB1 and inflammatory factors [tumor necrosis factor alpha (TNF-α)/interleukin-1beta (IL-1β)/IL-10] were assessed by RT-qPCR/ELISA, followed by comparisons of oxidative stress indices [glutathione-peroxidase (GSH-Px)/catalase (CAT)/superoxide dismutase (SOD)] using a fully automatic biochemical analyzer. Correlations between serum miR-582-5p with serum HMGB1, and between their levels with TNF-α/IL-1β/IL-10 were analyzed by Pearson analysis. The NIHSS score/Barthel Index scale were used to assess neurological function/daily living ability. Intervention safety for ACI patients was evaluated., Results: RIPC intervention increased serum miR-582-5p levels and decreased serum HMGB1 levels in ACI patients. RIPC intervention significantly reduced inflammation (diminished TNF-α/IL-1β levels, increased IL-10 level) and oxidative stress (elevated GSH-Px/CAT/SOD levels) in ACI patients. Serum miR-582-5p was negatively correlated with TNF-α and IL-1β levels, while positively correlated with IL-10 level, while HMGB1 was positively correlated with TNF-α and IL-1β levels, while negatively correlated with IL-10 level. miR-582-5p was negatively correlated with HMGB1. RIPC intervention improved neurological function (reduced NIHSS, increased Barthel scores) in ACI patients to some extent. RIPC had certain effectiveness and safety in the treatment of ACI., Conclusion: After RIPC intervention, serum miR-582-5p levels were increased, HMGB1 levels were decreased, and inflammation and oxidative stress were reduced in ACI patients, which mitigated neurological deficits, improved patients' ability to perform life activities, and exerted neuroprotective effects to some extent., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The risk of an anastomotic leakage (AL) following Ivor-Lewis esophagectomy is increased in patients with calcifications of the aorta or a stenosis of the celiac trunc. Ischemic conditioning (ISCON) of the gastric conduit prior to esophagectomy is supposed to improve gastric vascularization at the anastomotic site. The prospective ISCON trial was conducted to proof the safety and feasibility of this strategy with partial gastric devascularization 14 days before esophagectomy in esophageal cancer patients with a compromised vascular status. This work reports the results from a translational project of the ISCON trial aimed to investigate variables of neo-angiogenesis., Methods: Twenty esophageal cancer patients scheduled for esophagectomy were included in the ISCON trial. Serum samples (n = 11) were collected for measurement of biomarkers and biopsies (n = 12) of the gastric fundus were taken before and after ISCON of the gastric conduit. Serum samples were analyzed including 62 different cytokines. Vascularization of the gastric mucosa was assessed on paraffin-embedded sections stained against CD34 to detect the degree of microvascular density and vessel size., Results: Between November 2019 and January 2022 patients were included in the ISCON Trial. While serum samples showed no differences regarding cytokine levels before and after ISCON biopsies of the gastric mucosa demonstrated a significant increase in microvascular density after ISCON as compared to the corresponding gastric sample before the intervention., Conclusion: The data prove that ISCON of the gastric conduit as esophageal substitute induces significant neo-angiogenesis in the gastric fundus which is considered as surrogate of an improved vascularization at the anastomotic site., Competing Interests: Declaration of competing interest All authors declare that there are no conflicts of interest related to this manuscript., (© 2023 Published by Elsevier Ltd.)

Purpose: Free muscular flaps are commonly used in plastic surgery. The main reason of failure is thrombosis induced by a phenomenon called ischemia reperfusion. Preconditioning showed an interest to prevent ischemia reperfusion injury in transplantation surgery. The aim of the study is to evaluate the effect of ischemic preconditioning on skeletal tissue tolerance after warm venous ischemia., Materials and Methods: We realized an experimental study with latissimus dorsi flaps of 12 pigs, divided in 6 groups in function of their time of preconditioning and duration of warm venous ischemia. A morphologic analysis was performed measuring cell's diameter and interstitial tissue area and notifying the presence or absence of neutrophils, necrosis or intravascular thrombosis. To detect inflammation, necrosis or hypoxia, immunohistochemistry was effectuated using the follow primary antibodies, AIF, HIF1 alpha, caspase 3, SOD 1 and PKC epsilon. TUNEL assay showed apoptosis cells, were realized. One way Anova test was performed to compare the quantitative evolution over time of histological parameters and rate of apoptosis., Results: Preconditioning of 40min or 1hour allowed to reduced ischemia reperfusion lesions: no cellular or interstitial oedema, reduction of neutrophils infiltrate and intravascular thrombus. TUNEL assay showed a higher rate of apoptosis nucleus for the control group E compared to preconditioning group C and D. Immunohistochemistry results were no relevant., Conclusion: We showed a diminution of lesions of ischemia reperfusion for experimental groups with preconditioning: diminution of interstitial oedema, of cellular oedema, diminution of neutrophils infiltrated and level of apoptosis cells. Preconditioning of 40minutes were as efficient as one hour., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Contrast-induced nephropathy (CIN) is a major inconvenience in the use of iodinated contrast media (ICM) and it is associated with a significant increase in morbidity and mortality and cost of hospitalization. Remote ischemic preconditioning (RIPC) is a noninvasive and cost-effective tissue protection technique that has showed to be beneficial in decreasing renal insult in patients receiving intravascular contrast., Aim: The primary outcome of this study is to evaluate the impact of RIPC on the incidence of CIN in patients undergoing endovascular aneurysm repair., Methods: Patients suffering from aortic aneurysm were recruited prior to the administration of ICM. Randomization was used to assign patients into the control/RIPC groups. Biochemical parameters determined renal function before and after surgery in immediate (24-72 hr) and at 30 days of follow-up., Results: Of the 120 patients included in the study, 98,3% were male. Mean age was 73 years (range: 56-87 years). Diabetes and chronic renal failure (considering estimated glomerular filtration [eGFR] <60) was present prior to administration of ICM in 29.16% and 38.33%, respectively. RIPC was applied in 50% (n = 60) of the patients. A total of 24.17% developed CIN regardless of fluidotherapy, RIPC, and other protective strategies. RIPC did not influence outcomes in terms of incidence on CIN, serum creatinine, urea, eGFR, or microalbuminuria in immediate postoperative period. However, the group of RIPC patients showed a statistically significant benefit in renal function in terms of serum creatinine (1.46 ± 0.3 vs. 1.03 ± 0.5; P < 0.001), urea (61.06 ± 27.5 mg/dL vs. 43.78 ± 12.9 mg/dL; P = 0.003), and an increase in eGFR (56.37 ± 23.4 mL/min/1.73 m 2 vs. 72.85 ± 17.7 mL/min/1.73 m 2 ; P = 0.004) at 30 days of follow-up., Conclusions: RIPC seems to be a reasonable, effective, and low-cost technique to alleviate effects of ICM on the renal parenchyma in endovascular aneurysm repair procedures during short-term postoperative period., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: This review aims to highlight mechanistic insights on skeletal muscle ischemia/reperfusion injury (IRI), a potentially life-threatening complication after acute lower limb ischemia. Lower limb IRI produces a wide spectrum of manifestations, ranging from local skeletal muscle necrosis to multi-organ failure. There is increasing evidence from both in vitro and in vivo reports to demonstrate several promising interventions that have successfully reduced IRI in skeletal muscle ischemic models. However, clinical studies to confirm their benefits are still lacking., Methods: We conducted a comprehensive search of English literature listed in the PubMed database (All related published articles shown in PubMed until September 2020 have been included in this review), using the following keywords: acute limb ischemia, acute arterial occlusion, compartment syndrome, ischemic reperfusion injury, revascularization, and hypoxic reoxygenation., Results: A total of 58 articles pertinent to acute limb ischemia models were identified. The underlying mechanisms associated with IRI in skeletal muscle are due to excessive mitochondrial production of reactive oxygen species (ROS), cellular apoptosis and activation of inflammatory cascades. Several therapeutic interventions including both pharmacological and nonpharmacological treatments have been investigated and some showed promising results. These interventions include anti-oxidation, anti-inflammation, anti-hypertension, controlled-reperfusion, and ischemic preconditioning. Further clinical studies are needed to warrant their use in a clinical setting for lower limb IRI treatment., Conclusions: This review comprehensively summarizes the mechanisms underlying IRI in lower limb ischemia. The reports currently available regarding the potential therapeutic interventions against lower limb IRI from in vitro, in vivo and clinical studies are presented and discussed. These findings may provide mechanistic insights for devising the strategies to improve the clinical outcomes in IRI patients in the near future. Further clinical studies are needed to warrant their use in a clinical setting for lower limb IRI treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Remote ischemic preconditioning (RIPC) alleviates myocardial ischemia-reperfusion injury (IRI) that occurs during percutaneous coronary intervention (PCI) and increases the myocardial tolerance to ischemia and hypoxia. Prolonged inflation time of drug-coated balloons (DCBs) can improve the treatment effects of PCI and the long-term prognosis of patients. This study investigated whether preoperative RIPC improves the tolerance to extended DCB inflation time., Methods and Results: Overall, 345 patients with coronary artery disease (CAD) were enrolled; 90, 96, 83, and 76 of these were randomized into the upper limb RIPC, lower limb RIPC, upper limb control, and lower limb control groups, respectively. Their baseline data were collected. Data on cardiac markers were analyzed. The DCB inflation time was recorded. The baseline data and cardiac marker levels before operation did not differ between RIPC and control groups. The post-PCI high-sensitivity troponin-T levels were lower in the RIPC groups (35.81 ± 14.02 and 34.65 ± 14.86 pg/mL) than in the control groups (41.63 ± 18.31 and 42.24 ± 14.38 pg/mL) (P = 0.001). The DCB inflation tolerance time was higher in the lower limb RIPC group (120 s [120,120]) than in the upper limb RIPC group (120 s [110,120]), and was the lowest in the upper limb control (100 s [90, 120]) and the lower limb control (100 s [90, 115]) groups (P < 0.001)., Conclusions: RIPC reduces the level of myocardial damage that occurs during PCI and prolongs tolerance to increased DCB inflation time. The larger the ischemic area in RIPC, the better the improvement in the tolerance to extended DCB inflation time., (Copyright © 2022. Published by Elsevier B.V.)

Aims: We previously showed that hindlimb ischemia-reperfusion (IR) enhanced glucose uptake in the liver through the activation of the parasympathetic nervous system. Although we suggested that the key glucose transporter (GLUT) in this hepatic glucose uptake was GLUT4 by western blotting, the molecular weight of GLUT4 was nearly the same as that of GLUT2, which is predominantly expressed in the liver. We primarily conducted a histological evaluation to determine whether IR specifically accelerates the overexpression of GLUT4, rather than GLUT2, in the hepatocytes in vitro and in vivo., Main Methods: A total of 54 male C57BL/6J mice were used and subjected to 3 min hindlimb ischemia repeated three times with 3 min interval. Focusing on the area connecting portal and central veins, the GLUT4 and GLUT2 expression in the hepatocytes were examined by real-time PCR and immunohistochemically. Moreover, the alteration of GLUT4 and GLUT2 expression by acetylcholine in the primary hepatocytes were examined by immunofluorescence., Key Findings: IR significantly upregulated the GLUT4, rather than GLUT2, expression in both mRNA and protein in the liver. Histological examination revealed marked glycogen storage in zone1, the periportal area, coincident with the enhanced GLUT4 immunoreactivity, in the IR-treated liver. Incubation of primary hepatocytes with acetylcholine induced the appearance of GLUT4 on the membrane peripheries., Significance: The overexpression of GLUT4 on the membrane peripheries contributed to increasing glucose uptake found in IR-treated livers. This acceleration of glucose uptake via GLUT4 may induce marked glycogen storage in zone1 through energy production linked with increased glucose preference., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Non-invasive Remote Ischemic Conditioning (RIC) offers an approach to reduce tissue damage in various organs/tissues. Besides attenuation of Ischemia-Reperfusion injury (I/R), beneficial effects on cutaneous microcirculation of free microsurgical flaps have been reported. Given the recency of this technique, there are considerable gaps in the current understanding of its mechanism of action. As a result, clinical transfer of RIC is prolongated in several fields. We aimed to optimize the RIC protocol by examination of different RIC-cycle numbers and its effect on changes of cutaneous microcirculation and duration., Methods: 80 subjects were divided into groups (1, 3, 5, 7 RIC cycles). RIC was applied via an inflatable tourniquet. Cutaneous microcirculation was continuously assessed at the contralateral anterior lateral thigh utilizing a ©O2C-device continuously., Results: RIC caused significant and sustained changes in microcirculation. Four hours after completion of RIC, a maximum increase of +80.8% (CI 1.395-2.221) in blood flow and +23.5% (CI 1.098-1.372) in tissue oxygen saturation was measured (three-cycle group). A higher number of applied cycles was accompanied with significant higher mean pain., Conclusion: Acute improvement of cutaneous microcirculation due to RIC lasted for at least 4 h after completion of the RIC-protocol. Dose-dependent effects of RIC are likely. With regard to the increase in pain, we recommend a RIC protocol of 3 cycles for future clinical application., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The beneficial effect of remote ischemic preconditioning (RIP) on electrophysiological parameters resulting in lower inducibility and sustainability of atrial fibrillation (AF) in patients with paroxysmal AF has been recently demonstrated in a randomized trial. However, the potential clinical impact of RIP on persistent AF (CAF) has not been investigated. Therefore, we designed a randomized trial set in a setting of electrical cardioversion (CV) of early onset CAF., Aim: The aim of the study is to answer the following questions: I) Does RIP have impact on rate of spontaneous conversion into sinus rhythm (SR) within 24 h after first RIP intervention? II) Does RIP have the potential to improve the acute outcome of CV following a standardized protocol?, Methods: The presented study is a two-armed randomized, placebo-controlled, double-blinded, multi-center trial in a cohort of 588 patients with early onset CAF referred for electrical CV. The patients will undergo 3 sessions (immediately after randomization, the following morning, and directly before scheduled CV 24 h after randomization) of either RIP intervention or a sham procedure. The primary outcome of the study, i.e. documentation of SR 24 h after randomization as well secondary outcome i.e. stable SR first CV without usage of anti-arrhythmic drugs will be documented by 12-lead surface electrocardiography., Conclusion: Previously observed positive effect of RIP on atrial electrophysiology might be also implemented in a clinical setting of CV and therefore simplified and improve patient treatment., (Copyright © 2020. Published by Elsevier Ltd.)

Background: There is a lack of sufficient data regarding the protective effects of remote ischemic preconditioning (RIPC) in patients at risk of developing contrast-induced nephropathy (CIN). Thus, this study was conducted to determine whether RIPC as an adjunct to standard therapy prevents CIN in high-risk patients undergoing coronary intervention., Methods: In a single-center, double-blinded, randomized controlled trial, 162 patients who were at risk of CIN received standard hydration combined with RIPC or hydration with sham preconditioning. RIPC was accomplished by four cycles of 5 min ischemia and 5 min reperfusion of the forearm. The primary endpoint was a rise in serum creatinine (>0.5 mg/dL or >25%) from baseline to serum creatinine 48-72 h after contrast administration., Results: Of the 162 patients, 81 were randomly allocated to receive sham preconditioning and 81 to receive RIPC. Significantly reduced serum creatinine levels were observed in patients with a Mehran moderate risk allocated to sham group compared to the RIPC group (0.070 ± 0.16 mg/dL vs. 0.107 ± 0.13 mg/dL, p = 0.001). With regards to the primary endpoint, a significantly higher change in serum creatinine from baseline to 48-72 h was observed in the sham group compared to the RIPC group (0.023 ± 0.2 μmol/L vs -0.064 ± 0.1 μmol/L, p < 0.001)., Conclusion: RIPC as an alternative to standard therapy, improved serum creatinine levels after contrast administration in patients at risk of CIN. However, present data indicate that RIPC might have beneficial effects in patients with a moderate or high risk of CIN., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2020 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: Management of avulsion injuries remains a challenge due to necrosis. The aim of the present study is to create an experimental model reproducing an avulsion injury and investigate the effects of hyperoxygenated solution (HOS), a method of oxygen delivery that has been widely used in the therapy of ischaemia-hypoxia diseases, on avulsion injury flap survival in rats., Methods: Forty male rats were divided into four groups (n = 10 each). Dorsal random pattern flaps measuring 3 × 9 cm, including the panniculus carnosus, were elevated and run over by the skin avulsion model machine, and the flaps were then sutured into their original places. The sham+HOS and avulsion+HOS groups received intravenous HOS (20 ml/kg) each day for 7 days after the operation. The sham+saline and avulsion+saline groups received intravenous saline solution (20 ml/kg) each day for 7 days after the operation. Percutaneous O 2 pressure (TcpO 2 ) measurement , serial examinations of skin flap blood perfusion, skin flap survival evaluation and histopathology were performed to assess the efficacy of HOS on avulsion injury., Results: Compared to the avulsion+saline groups, TcpO 2 was significantly higher in the avulsion+HOS groups at 15, 30 and 60 min after infusion (P < 0.05). The blood perfusion of flaps in the avulsion+HOS group was higher than in the avulsion+saline group (P < 0.05). The survival rate was higher in the avulsion+HOS group than in the avulsion+saline group (P < 0.05), and the histopathology assays supported the data., Conclusion: We succeeded in developing an avulsion injury model and demonstrated that HOS could improve the survival of the avulsion injury flaps in rats by effectively increasing the local oxygen content and blood perfusion and ameliorating inflammatory damage., Competing Interests: Declaration of Competing Interest The authors have no financial interests to declare in relation to the content of this article., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The main aim of this study was to evaluate the effect of remote ischaemic preconditioning (RIPC) on preventing the leakage of cardiac damage biomarkers in patients undergoing vascular surgery., Methods: This is a randomised, sham-controlled, double-blinded, single-centre study. Patients undergoing open abdominal aortic aneurysm repair, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited non-consecutively. The RIPC protocol consisting of 4 cycles of 5 minutes of ischaemia, followed by 5 minutes of reperfusion, was applied. A RIPC or a sham procedure was performed noninvasively along with preparation for anaesthesia. High sensitivity troponin T level was measured preoperatively and 2, 8 and 24 hours after surgery and pro b-type natriuretic peptide was measured preoperatively and 24 hours after surgery., Results: There was significantly higher leakage of high sensitivity troponin T (peak change median 2 ng/L, IQR 0.9-6.2 ng/L vs 0.6 ng/L, IQR 0.7-2.1 ng/L, p = .0002) and pro b-type natriuretic peptide (change median 144 pg/mL, IQR 17-318 pg/mL vs 51 pg/mL, IQR 12-196 pg/mL, p = .02) in the sham group compared to the RIPC group., Conclusion: RIPC reduces the leakage of high sensitivity troponin T and pro b-type natriuretic peptide. Therefore, it may offer cardioprotection in patients undergoing non-cardiac vascular surgery. The clinical significance of RIPC has to be evaluated in larger studies excluding the factors known to influence its effect., (Copyright © 2019 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Local and remote ischemic preconditioning has been used as a protective intervention against ischemia/reperfusion (I/R) damage in several preclinical and clinical studies. However, its physiological mechanisms are not completely known. I/R increases the production of reactive oxygen species, which also serve as messengers for a variety of functions. Hypoxia-inducible factor 1 alpha (HIF-1α) is probably the most important transcription factor mediator of hypoxic signaling., Objective: We hypothesized that limb ischemic conditioning (LIC) induces a local oxidative/nitrosative stress and a correlated increase of HIF-1α plasma levels., Methods: An observational, prospective, and single-center study has been conducted in 27 healthy volunteers. LIC was applied: three cycles (5 min of ischemia followed by 5 min of reperfusion) using an ischemia cuff placed on the upper left arm. Time course of 8-isoprostane, nitrite, and HIF-1α levels was measured in blood plasma. Venous blood was sampled from the left arm before tourniquet inflation (basal) and after LIC: 1 min and 2 hr for 8-isoprostane and nitrite; and 1 min, 2 hr, 8 hr, 24 hr, and 48 hr for HIF-1α., Results: After LIC, we have found an early increase of 8-isoprostane and nitrite. HIF-1α increased at 2 and 8 hr after LIC. We found a direct correlation between HIF-1α and 8-isoprostane and nitrite plasma levels., Conclusions: We concluded that LIC induces an early oxidative/nitrosative stress in the arm followed by an increase of HIF-1α plasma levels correlated with 8-isoprostane and nitrite levels, possibly as a local response., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Whether remote ischemic preconditioning (RIPC), through several cycles of ischemia-reperfusion, can generate endogenous protective substances to protect patients undergoing elective major vascular surgery remains unclear. The results derived from many randomized controlled trials (RCTs) have been discrepant., Methods: PubMed (1966 to May 2018) and EMBASE (1966 to May 2018) databases were searched to identify all published RCTs that assessed the effect of RIPC in patients undergoing elective major vascular surgery. Then, we performed a systematic review and meta-analysis to merge the outcomes of RIPC procedures from each RCT, which included all-cause mortality, myocardial infarction (MI), acute kidney injury (AKI), and/or new-onset arrhythmia., Results: A total of 909 patients were enrolled from 10 eligible studies that were conducted from 2007 through 2016. A fixed effect model was utilized in this study to pool each effect size. Pooled analyses of all RCTs showed that RIPC did not reduce the incidence of all-cause mortality (pooled risk ratio [RR] 1.36, 95% confidence interval [CI] 0.63-2.92, P = 0.56), MI (pooled RR 0.77, 95% CI 0.48-1.22, P = 0.38), AKI (pooled RR 0.93, 95% CI 0.68-1.27, P = 0.10), or new-onset arrhythmia (pooled RR 1.47, 95% CI 0.83-2.60, P = 0.52) compared with the control treatment. The publication bias detected by Begg's test was low., Conclusions: There is no prominent evidence to support the hypothesis that RIPC can provide perioperative protection to patients undergoing elective major vascular surgery. Therefore, the routine use of RIPC to reduce the incidence of perioperative complications of these operations may not be recommended., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Remote ischaemic preconditioning (RIPC) is a phenomenon that promotes protection of tissues and organs against ischaemia reperfusion injury. RIPC has been shown to reduce myocardial and renal injury but its effect on arterial stiffness in patients undergoing lower limb digital subtraction angiography (DSA) is unknown. The aim of this study was to evaluate the effect of RIPC on arterial stiffness in patients with peripheral arterial disease (PAD) undergoing lower limb DSA., Methods: In the RIPC intervention, the blood pressure cuff on the arm was inflated to 200 mmHg or to 20 mmHg above systolic pressure, and in the sham intervention to 20 mmHg. For both, the procedure was repeated for four five minute cycles at five minute intervals between the cycles. Changes in heart rate corrected augmentation index (AIx@75), augmentation index (AIx), carotid femoral pulse wave velocity (PWV), and haemodynamic parameters were measured before and 24 h after DSA., Results: 111 (RIPC 54, sham 57) patients with symptomatic lower limb PAD scheduled for DSA were randomised. 102 patients (RIPC 47, sham 55) were included in final analysis. RIPC significantly improved AIx (-5.46% in RIPC and -1.45% in sham group; p = .05), but not AIx@75 (-4.88% in RIPC and -1.38% in sham group; p = .07) or PWV (-0.41 m/s in RIPC and -0.27 m/s in sham group; p = .74). In the RIPC group a significant reduction in AIx (p = .002) and AIx@75 (p = .003) was noted after stenting when compared with the sham intervention. AIx (p = .001), AIx@75 (p = .002), mean arterial (p = .01), peripheral (p = .02), and central systolic blood pressure (p = .006) were significantly reduced only in the RIPC group 24 h after DSA., Conclusion: This study evaluates for the first time the effects of RIPC on arterial stiffness parameters in patients with symptomatic PAD following DSA. RIPC may modulate arterial stiffness following a DSA procedure and is more pronounced in patients after stent placement., (Copyright © 2019 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: The REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) RCT examined whether remote ischaemic preconditioning (RIPC) improved renal function after living-donor kidney transplantation. The primary endpoint, glomerular filtration rate (GFR), quantified by iohexol at 12 months, suggested that RIPC may confer longer-term benefit. Here, we present yearly follow-up data of estimated GFR for up to 5 yr after transplantation., Methods: In this double-blind, factorial RCT, we enrolled 406 adult live donor kidney transplant donor-recipient pairs in 15 European transplant centres. RIPC was performed before induction of anaesthesia. RIPC consisted of four 5 min inflations of a BP cuff on the upper arm to 40 mm Hg above systolic BP separated by 5 min periods of cuff deflation. For sham RIPC, cuff inflation to 40 mm Hg was undertaken. Pairs were randomised to sham RIPC, early RIPC only (immediately pre-surgery), late RIPC only (24 h pre-surgery), or dual RIPC (early and late RIPC). The pre-specified secondary outcome of estimated GFR (eGFR) was calculated from serum creatinine measurements, using the Chronic Kidney Disease Epidemiology Collaboration equation. Predefined safety outcomes were mortality and graft loss., Results: There was a sustained improvement in eGFR after early RIPC, compared with control from 3 months to 5 yr (adjusted mean difference: 4.71 ml min -1 (1.73 m) -2 [95% confidence interval, CI: 1.54-7.89]; P=0.004). Mortality and graft loss were similar between groups (RIPC: 20/205 [9.8%] vs control 24/201 [11.9%]; hazard ratio: 0.79 [95% CI: 0.43-1.43])., Conclusions: RIPC safely improves long-term kidney function after living-donor renal transplantation when administered before induction of anaesthesia., Clinical Trial Registration: ISRCTN30083294., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: While the perioperative stroke rate after carotid endarterectomy (CEA) is low, "silent" microinfarctions identified by magnetic resonance imaging (MRI) are common and have been correlated with postoperative neurocognitive decline. Our study will investigate the role of remote ischemic preconditioning (RIPC) as a potential neuroprotective mechanism. RIPC is a well-tolerated stimulus that, through neuronal and humoral pathways, generates a systemic environment of greater resistance to subsequent ischemic insults. We hypothesized that patients undergoing RIPC before CEA will have improved postoperative neurocognitive scores compared with those of patients undergoing standard care., Methods: Patients undergoing CEA will be randomized 1:1 to RIPC or standard clinical care. Those randomized to RIPC will undergo a standard protocol of 4 cycles of RIPC. Each RIPC cycle will involve 5 min of forearm ischemia with 5 min of reperfusion. Forearm ischemia will be induced by a blood pressure cuff inflated to 200 mm Hg or at least 15 mm Hg higher than the systolic pressure if it is >185 mm Hg. This will occur after anesthesia induction and during incision/dissection but before manipulation or clamping of the carotid; thus, patients will be blinded to their assignment. Before carotid endarterectomy, all patients will undergo baseline neurocognitive testing in the form of a Montreal Cognitive Assessment (MoCA) and National Institutes of Health (NIH) Toolbox. MoCA testing only will be conducted on postoperative day 1 in the hospital. The full neurocognitive testing battery will again be conducted at 1-month follow-up in the office. Changes from baseline will be compared between arms at the follow-up time points. Assuming no drop-ins or dropouts and a 10% loss to follow-up, we would need a sample size of 43 patients for 80% power per treatment arm. The primary endpoint, change in MoCA scores, will be analyzed using a random effects model, and secondary outcomes will be analyzed using either linear or logistic regression where appropriate., Conclusions: RIPC, if shown to be effective in protecting patients from neurocognitive decline after CEA, represents a safe, inexpensive, and easily implementable method of neuroprotection., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Hydrogen gas exists in the atmosphere and was previously considered an inert gas. It has been reported to have protective effects on tissue ischemia-reperfusion (IR) injuries in animal models. The protective mechanism of hydrogen molecules is based on selectively reducing highly strong oxidants in cells, thereby reducing inflammation and decreasing the contents of MDA, FOXO3a, and other pathways that result in flap necrosis. Previous studies were conducted with postconditioning with hydrogen. In this article, we want to investigate whether inhalation of hydrogen has a preventive effect on IR injury., Methods: Forty-five adult male Sprague Dawley rats (body weight 220-250 g) were randomly divided into three groups: (1) Sham operation group (SH), (2) Ischemia-reperfusion injury group (IR), and (3) Ischemia-reperfusion injury with preconditioning hydrogen group (PRH). IR injury was induced by clamping the right superficial epigastric artery for 3 h. Before undergoing 3 h of IR management, the PRH group was treated with hydrogen inhalation for 1 h. On the third postoperative day, survival area and blood perfusion of the flap were assessed using laser Doppler flowmetry. RIP1 and RIP3 were examined by immunological detection and western blot analysis., Results: Both the IR and PRH groups had less skin flap survival area and less blood perfusion than the sham group (P < 0.05). RIP1 and RIP3 were highly expressed in the IR and PRH groups when compared with those in the SH group (P < 0.05). There were no significant differences in flap survival rate (32.34 ± 2.19% and 33.09 ± 1.64%), average blood perfusion (41.66 ± 3.53 pu, 48.57 ± 2.83 pu), and expression of RIP1 and RIP3 (0.5167 ± 0.1409 and 0.4693 ± 0.1454) between the IR and PRH groups., Conclusions: Preconditioning with one-time inhaled hydrogen does not attenuate skin flap IR injuries in rat models., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Remote ischemic preconditioning (RIPC) is a method of preparing the body for a later prolonged ischemic episode to protect against subsequent detrimental effects. This study aimed to identify the effects of RIPC in vascular surgery., Methods: A standard Preferred Reporting Items for Systematic Reviews and Meta-Analyses search was conducted of randomized controlled trials of RIPC in patients undergoing open or endovascular aneurysm repair, carotid endarterectomy, or lower limb bypass reporting on mortality and renal or cardiac outcomes. Random-effects meta-analysis was performed using Review Manager 5.3 (The Nordic Cochrane Center, Copenhagen, Denmark)., Results: A total of 13 randomized controlled trials in the meta-analysis included 548 patients in the RIPC cohort and 549 controls. There was no significant difference in mortality, renal dysfunction, myocardial infarction, myocardial injury, or length of stay between the groups, with subgroup and sensitivity analysis showing no significant difference., Conclusions: Current evidence demonstrates no benefit of RIPC in vascular surgery. Further large multicenter trials of RIPC in major vascular surgery should be considered., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: During hepatectomy, intermittent portal triad clamping (IPC) reduces ischemia-reperfusion injuries. Pharmacological preconditioning with sevoflurane revealed similar properties. The aim of the study was to evaluate the combination of a sevoflurane preconditioning regimen with IPC on ischemia-reperfusion injuries., Methods: Three regimens of anesthesia were applied: group SEV with continuous application of sevoflurane, group PRO with continuous propofol infusion and group PC where continuous propofol was substituted by sevoflurane (adjusted to reach MAC∗1.5) for 15 min before IPC. Endpoints were the values of AST and ALT, factor V, prothrombin time, bilirubinemia over the 5-postoperative days (POD), morbidity and mortality at POD30 and POD90., Results: The ALT values at POD5 were lower in the PC group (n = 27) 74 (48 -98) IU/L compared to PRO (n = 26) and SEV (n = 67) respectively 110 (75 -152) and 100 (64 -168) IU/L (p = 0.038). The variation of factor V compared to preoperative values was less important in the PC and SEV groups respectively -14% and -16% vs -30% (PRO) (p = 0.047)., Conclusion: Our study suggests that sevoflurane attenuates ischemia-reperfusion injuries on liver function, compared to propofol, without benefit for a specific regimen of pharmacological preconditioning when IPC is applied., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Ischemic stroke and reperfusion injury are a common and serve medical situation in the elderly population. H 2 S is a gas neuromodulator which also possesses anti-oxidant and anti-inflammatory properties, and is found to play neuroprotective effect in neurodegenerative diseases. This study investigated the effect of endogenous and exogenous H 2 S in a mouse model of ischemic stroke. 129P2-Cbs tm1Unc /J mice with heterozygous mutants in H 2 S generating enzyme cystathionine β-synthase were used to study the effect of endogenous H 2 S. H 2 S donor NaHS was used as exogenous H 2 S. Animals were pretreated with H 2 S and then subjected to middle cerebral artery occlusion surgery. Behavioral outcome was evaluated by novel object recognition test. Inflammatory cytokines were measured using ELISA. Western blot was used to detect the activation of NF-κB. Aged 129P2-Cbs tm1Unc /J mice showed exaggerated inflammation and more severe cognitive impairment after ischemia, while exogenous H 2 S treatment inhibited inflammation and attenuated behavioral impairment. The anti-inflammatory effect of H 2 S was mediated by inhibiting NF-κB. Our findings suggest that both endogenous and exogenous H 2 S are involved in the neuroprotection against ischemia/reperfusion-induced cerebral injury., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Remote ischaemic preconditioning (RIPC) consists of repeated cycles of limb ischaemia and reperfusion, which may reduce perioperative myocardial ischaemic damage and kidney injury. We hypothesised that RIPC may be beneficial by attenuating the systemic inflammatory response. We investigated whether RIPC affects the response in humans to bacterial endotoxin (lipopolysaccharide [LPS]) by measuring plasma cytokines and renal cell-cycle arrest mediators, which reflect renal tubular stress., Methods: Healthy male volunteers were randomised to receive either daily RIPC for 6 consecutive days (RIPC multiple , n=10) plus RIPC during the 40 min preceding i.v. LPS (2 ng kg -1 ), RIPC only during the 40 min before LPS (RIPC single , n=10), or no RIPC preceding LPS (control, n=10). As a surrogate marker of renal tubular stress, the product of urinary concentrations of two cell-cycle arrest markers was calculated (tissue inhibitor of metalloproteinases-2 [TIMP2]*insulin-like growth factor binding protein-7 [IGFBP7]). Data are presented as median (inter-quartile range)., Results: In both RIPC groups, RIPC alone increased [TIMP2]*[IGFBP7]. LPS administration resulted in fever, flu-like symptoms, and haemodynamic alterations. Plasma cytokine concentrations increased profoundly during endotoxaemia (control group: tumor necrosis factor alpha [TNF-α] from 14 [9-16] pg ml -1 at baseline to 480 [284-709] pg ml -1 at 1.5 h after LPS; interleukin-6 [IL-6] from 4 [4-4] pg ml -1 at baseline to 659 [505-1018] pg ml -1 at 2 h after LPS). LPS administration also increased urinary [TIMP2[*[IGFBP7]. RIPC had no effect on LPS-induced cytokine release or [TIMP2]*[IGFBP7]., Conclusions: RIPC neither modulated systemic cytokine release nor attenuated inflammation-induced tubular stress after LPS. However, RIPC alone induced renal markers of cell-cycle arrest., Clinical Trial Registration: NCT02602977., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: The main aim of this study was to evaluate the effect of remote ischaemic preconditioning (RIPC) on arterial stiffness in patients undergoing vascular surgery., Methods: This was a randomised, sham controlled, double blind, single centre study. Patients undergoing open abdominal aortic aneurysm repair, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited. A RIPC or a sham procedure was performed, using a blood pressure cuff, along with preparation for anaesthesia. The RIPC protocol consisting of four cycles of 5 min of ischaemia, followed by 5 min of reperfusion was applied. Arterial stiffness and haemodynamic parameters were measured pre-operatively and 20-28 h after surgery. Two primary outcomes were selected: augmentation index and pulse wave velocity., Results: Ninety-eight patients were randomised. After dropouts 44 and 46 patients were included in the RIPC and sham groups, respectively. Both groups were comparable. There were no statistically significant differences in augmentation index (p = .8), augmentation index corrected for heart rate of 75 beats per minute (p = .8), pulse wave velocity (p = .7), large artery elasticity indices (p = .8), small artery elasticity indices (p = .6), or mean arterial pressure (p = .7) changes between the RIPC and sham groups. There occurred statistically significant (p ≤ .01) improvement in augmentation index (-5.8% vs. -5.5%), augmentation index corrected for a heart rate of 75 beats per minute (-2.5% vs. -2%), small artery elasticity indices (0.7 mL/mmHg × 100 vs. 0.9 mL/mmHg × 100), and mean arterial pressure post-operatively in both the RIPC and the sham groups (change median values in RIPC and sham groups, respectively)., Conclusions: RIPC had no significant effect on arterial stiffness, but there was significant improvement in arterial stiffness after surgery in both groups. Arterial stiffness and haemodynamics may be influenced by surgery or anaesthesia or oxidative stress or all factors combined. Further studies are needed to clarify these findings. CLINICALTRIALS.GOV: NCT02689414., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Animal data suggest that remote ischemic conditioning (RIC) can improve blood flow in ischemic limbs and, consequently, may benefit claudication patients. Supervised exercise is the preferred first-line intervention for patients with intermittent claudication (IC) but is constrained by limited availability and logistical issues, particularly in rural settings. The aim of this study is to evaluate remote ischemic pre-conditioning in the management of intermittent claudication patients., Methods: We undertook a randomized clinical trial to evaluate RIC's effect in claudication patients. Stable IC patients were randomly allocated to receive RIC alone, structured exercise (SE) alone, RIC plus SE, or to a control group which received standard advice and risk factor modification. Patients received their intervention over a 28-day period. RIC patients attended an RIC clinic every 3-4 days to undergo 4 cycles of 5-min upper limb ischemia followed by 5-min reperfusion induced with a standard blood pressure cuff., Results: Forty-five patients were randomized, of whom 40 completed the trial (10 patients per group). The RIC alone, SE alone, and RIC plus SE groups all demonstrated significant improvements in pain-free walking distance and ankle-brachial pressure indices at 30 days. There were no differences in the magnitude of improvements between the groups., Conclusions: Compared with standard care RIC is promising as a home-delivered intervention. It appears to be equivalent to SE in the treatment of IC, with no apparent additive benefit to combining the 2 interventions in this small size sample. Large-scale randomized controlled trial is needed for validation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Testicular torsion is a surgical emergency mainly affecting adolescent boys, with a relatively high rate of missed torsion and testicular loss secondary to delay in prompt diagnosis and surgical intervention. With ischemic reperfusion injury as its underlying culprit, testicular torsion may respond favorably to remote ischemic conditioning (RIC) where a non-privileged site (e.g. limb) is concurrently rendered ischemic to divert the cascade of reperfusion injury from the privileged organ (e.g. testicle), thus offering a protective effect in improving salvage. This mechanism is established for other organs, whereas it has not been evaluated for testis., Aim: It was aimed to evaluate RIC in a rat model of testicular torsion as a proof of principle that, similar to what has been demonstrated in other organs, RIC does offer testicular protection., Study Design: This is an animal experimental study. Thirty Sprague-Dawley male rats were divided into control group (n = 15) and experimental group (n = 15). Non-survival surgeries of right-sided spermatic cord torsion (720° counter-clockwise twist) were performed for both the groups (45 min) followed by detorsion and reperfusion (5 min) and then orchiectomy. For the experiment group, an intervention of tail clamping to create RIC was applied 5 min after torsion, then unclamping 5 min before detorsion, followed by detorsion and reperfusion for 5 min and then orchiectomy. The testicles were histologically and immunologically examined using a hypoxia inducible factor (HIF-1α) ELISA Kit. The histological findings on ischemic changes, vascular congestion, and immunohistochemistry were quantified using previously described, validated grading systems., Results: DISCUSSION: This is the first study to demonstrate the concept of RIC in an animal model of testicular torsion. It is limited by the non-availability of similar studies to compare outcomes and by the caution of extrapolating animal studies on humans. It does lay grounds, however, to subsequent studies to further elaborate on this concept and its clinical applicability., Conclusion: When RIC is applied in the experimental setting of testicular torsion, there is less evidence of hypoxic injury by histology and immunohistochemistry., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Repeated remote ischaemic conditioning (RIC) during weaning from cardiopulmonary bypass and in the early postoperative period may confer protection against acute kidney injury (AKI). We evaluated the effect of repeated RIC on the incidence of AKI in patients undergoing valvular heart surgery., Methods: Patients were randomised into either the RIC (n=120) or control (n=124) group. A pneumatic tourniquet was placed on each patient's thigh. Upon removal of the aortic cross-clamp, three cycles of inflation for 5 min at 250 mm Hg (with 5 min intervals) were applied in the RIC group. Additionally, three cycles of RIC were repeated at postoperative 12 and 24 h. AKI was diagnosed based on the Kidney Disease: Improving Global Outcomes guideline. The incidences of renal replacement therapy, permanent stroke, sternal wound infection, newly developed atrial fibrillation, mechanical ventilation >24 h, and reoperation for bleeding during hospitalisation were recorded., Results: The incidences of AKI were not significantly different between the control (19.4%) and RIC (15.8%) groups (a difference of 3.5 percentage points; 95% confidence interval: -6.8%-13.9%; P=0.470). Perioperative serum creatinine concentrations were similar in the control and RIC groups (P=0.494). Fluid balance, urine output, blood loss, transfusion, and vasopressor/inotropic requirements were not significantly different between the groups (all P>0.05). The occurrences of a composite of morbidity and mortality endpoints were not significantly different between the control (46.0%) and RIC (39.2%) groups (a difference of 6.8 percentage points; 95% confidence interval: -6.4%-20.0%; P=0.283)., Conclusions: The results of our study do not support repeated RIC to decrease the incidence of AKI after valvular heart surgery., Clinical Trial Registration: NCT02720549., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: To study if four cycles of remote ischemic preconditioning (RIPC) could offer protection against contrast induced nephropathy (CIN) and post procedural renal dysfunction in high risk patients undergoing percutaneous coronary intervention (PCI)., Methods: This was a prospective single blind randomized sham controlled trial where patients undergoing coronary angioplasty with stage III chronic kidney disease were randomized into sham preconditioning and remote ischemic preconditioning. The primary outcome was the reduction in the incidence of CIN. The secondary outcomes were the maximum improvement in eGFR, maximum reduction in serum creatinine and composite of requirement of hemodialysis, death and rehospitalization for heart failure up to 6 weeks after PCI., Results: Eleven out of fifty patients in the study group developed CIN (22%) compared to eighteen out of the fifty control patients (36%) (p=0.123). There was a statistically significant improvement in the post procedure creatinine values at 24h (p=0.013), 48h (p=0.015), 2 weeks (p=0.003), 6 weeks (p=0.003) and post procedure glomerular filtration rate (eGFR) values at 24h (p=0.026), 48h (p=0.044), 2 weeks (p=0.015) and 6 weeks (p=0.011) in study group compared to control group. The secondary outcome composite of requirement of hemodialysis, death and rehospitalization for heart failure was not statistically significant (p: 0.646)., Conclusion: RIPC does not result in significant reduction of CIN. However RIPC helps in the prevention of post procedural worsening in eGFR and serum creatinine even up to 6 weeks., (Copyright © 2017. Published by Elsevier B.V.)

Acute kidney injury (AKI) is a major public health concern, which is contributing to serious hospital complications, chronic kidney disease (CKD) and even death. Renal ischemia-reperfusion injury (IRI) remains a leading cause of AKI. The stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against renal IRI and may be preventively induced using hemin prior to renal insult. This HO-1 induction pathway called hemin preconditioning is largely known to be effective. Therefore, HO-1 might be an interesting therapeutic target in case of predictable AKI (e.g. partial nephrectomy or renal transplantation). However, the use of hemin to mitigate established AKI remains poorly characterized. Mice underwent bilateral renal IRI for 26 min or sham surgery. After surgical procedure, animals were injected either with hemin (5 mg/kg) or vehicle. Twenty-four hours later, mice were sacrificed. Despite strong HO-1 induction, hemin-treated mice exhibited significant renal damage and oxidative stress as compared to vehicle-treated mice. Interestingly, higher dose of hemin is associated with more severe IRI-induced AKI in a dose-dependent relation. To determine whether hemin preconditioning remains efficient to dampen postoperative hemin-amplified IRI-induced AKI, we pretreated mice either with hemin (5 mg/kg) or vehicle 24 h prior to surgical procedure. Then, all mice (hemin- and vehicle-pretreated) received postoperative injection of hemin (5 mg/kg) to amplify IRI-induced AKI. In comparison to vehicle, prior administration of hemin to renal IRI mitigated hemin-amplified IRI-induced AKI as attested by fewer renal damage, inflammation and oxidative stress. In conclusion, hemin may have a dual effect on renal IRI, protective or deleterious, depending on the timing of its administration., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: The objective of the present study was to evaluate the protective effect of pre-conditioning treatment with laser light on hepatic injury in rats submitted to partial ischemia using mitochondrial function and liver fatty acid binding protein as markers., Methods: Rats were divided into four groups (n=5): 1) Control, 2) Control + Laser, 3) Partial Ischemia and 4) Partial Ischemia + Laser. Ischemia was induced by clamping the hepatic pedicle of the left and middle lobes of the liver for 60 minutes. Laser light at 660 nm was applied to the liver immediately prior to the induction of ischemia at 22.5 J/cm2, with 30 seconds of illumination at five individual points. The animals were sacrificed after 30 minutes of reperfusion. Blood and liver tissues were collected for analysis of mitochondrial function, determination of malondialdehyde and analysis of fatty acid binding protein expression by Western blot., Results: Mitochondrial function decreased in the Partial Ischemia group, especially during adenosine diphosphate-activated respiration (state 3), and the expression of fatty acid binding protein was also reduced. The application of laser light prevented bioenergetic changes and restored the expression of fatty acid binding protein., Conclusion: Prophylactic application of laser light to the livers of rats submitted to partial ischemia was found to have a protective effect in the liver, with normalization of both mitochondrial function and fatty acid binding protein tissue expression.

Background: Remote ischemic preconditioning (RIPC) is a mechanism to protect tissues from injury during ischemia and reperfusion. We investigated the neuroprotective effects of RIPC in neonates undergoing cardiac surgery., Methods: The outcome was white matter injury (WMI), assessed by the change in volume of WMI from preoperative to postoperative brain magnetic resonance imaging (MRI). Patients were randomized to RIPC or SHAM. RIPC was induced prior to cardiopulmonary bypass by four 5-minute cycles of blood pressure cuff inflation to produce ischemia of the lower extremity. For patients randomized to SHAM, the cuff was positioned, but not inflated., Results: The study included 67 patients, with 33 randomized to RIPC and 34 randomized to SHAM. Preoperative and postoperative MRIs were available in 50 patients, including 26 of the 33 RIPC patients and 24 of the 34 SHAM patients. There were no differences in baseline and operative characteristics for either the overall study group or the group with evaluable MRIs. WMI was identified in 28% of the patients preoperatively and in 62% postoperatively. There was no difference in the prevalence of WMI by treatment group (p > 0.5). RIPC patients had an average change in WMI of 600 mL 3 , and SHAM subjects had an average WMI change of 107 mL 3 . There was no significant difference in the mean value of WMI change between patients who received RIPC and those who received SHAM treatments (p = 0.178)., Conclusions: In this randomized, blinded clinical trial, there was no evidence that use of RIPC provides neuroprotection in neonates undergoing repair of congenital heart defects with cardiopulmonary bypass., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To study the effects of intermittent whole-body hypoxic preconditioning on patients with carotid artery stenosis., Methods: Fifty patients with carotid artery stenosis were selected and randomly divided into a hypoxic intervention group (HIG) and a control group (CG). Both groups were treated with a hypoxic respiration device for 7 days (HIG: 18% oxygen, CG: 21% oxygen). Venous blood samples were taken preoperatively and postoperatively. The subjects' vital signs were recorded during and after the intervention. After the completion of the trial, the concentrations of hemoglobin, hypoxia inducible factor-1α, erythropoietin, vascular endothelial growth factor, neuron-specific enolase, S100β protein, brain-derived neurotrophic factor, serum aspartate transaminase, serum alanine aminotransferase, serum creatinine, and blood urea nitrogen were measured in the previously selected blood samples., Results: During the intervention, the vital signs of the HIG were significantly different from those of the CG (P < 0.05). In the HIG, postoperative concentrations of hemoglobin, erythropoietin, hypoxia inducible factor-1α, and vascular endothelial growth factor were significantly more than the preoperative values (P < 0.05). In the CG, postoperative concentrations of neuron-specific enolase and S100β protein were more than the preoperative values (P < 0.05). The concentrations of brain-derived neurotrophic factor, serum aspartate transaminase, serum alanine aminotransferase, serum creatinine, and blood urea nitrogen showed no significant differences between their preoperative and postoperative values in either the HIG or the CG (P > 0.05)., Conclusions: Intermittent hypoxic preconditioning can change the vital signs and hematologic indexes of patients with carotid artery stenosis without causing new postoperative complications or organ damage., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The potential protective effects of remote ischemic preconditioning (RIPC) on contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) remain to be defined., Methods and Results: A double blind, randomized, placebo controlled multicenter study was performed. Patients younger than 85years old, with a renal clearance of 30-60ml/min/1.73m 2 , who were candidates for PCI for all clinical indications except for primary PCI, were allocated 1:1 to RIPC or to standard therapy. The primary endpoint was incidence of CIN. The secondary endpoint was incidence of peri-procedural myocardial infarction (PMI). From February 2013 to April 2014, 3108 patients who were scheduled for coronary angiography were screened for the study. 442 fulfilled the inclusion criteria and 223 received PCI. These patients were randomized to sham RIPC (n=107) or treatment group (n=116). The only pre-specified subgroup of diabetic patients included 85 (38%) cases. RIPC significantly reduced CIN incidence in the overall population (12.1% vs. 26.1%, p=0.01, with a NNT=9) and in non-diabetic patients (9.2% vs. 25.0%, p=0.02), but showed no benefit in diabetics (16.7% vs. 28.2%, p=0.21). A trend for lower PMI was seen in the intervention arm (creatine kinase - muscle brain >5 URL; 8.4% vs. 16.4%, p=0.07; troponin T >5 URL; 27% vs. 38%, p=0.21)., Conclusions: Remote ischemic preconditioning significantly reduces the incidence of acute kidney injury in non-diabetic patients undergoing PCI. Larger sample size is presumably needed to assess the effect of RIPC for patients with diabetes mellitus. Clinical Trial number:NCT02195726https://www.clinicaltrial.gov/., (Copyright © 2017. Published by Elsevier B.V.)

Background: Temporary hepatic ischemia is inevitable during open aortic surgery when supraceliac clamping is necessary, as in thoracoabdominal or pararenal aneurysms. Remote ischemic preconditioning (RIPC) has been described as a potential protective means against ischemia-reperfusion injury (IRI) in various tissues including the liver. The aim of this experimental study was to detect the effect of RIPC on liver IRI in a model of supraceliac aortic cross-clamping., Methods: An animal study was performed. Four groups of 6 swines each were examined: the control (sham) group, the ischemia-reperfusion (IR) group, and 2 remote ischemic preconditioning groups (RIPC I and RIPC II group). In the IR group, the animals underwent a complete cessation of the splanchnic arterial circulation for 30 min by a concomitant occlusion of the supraceliac and the infrarenal aorta. In the RIPC groups, a remote preconditioning was applied before the splanchnic ischemia. This consisted of a temporary occlusion of the infrarenal aorta for 15 min followed by 15 min of reperfusion (RIPC I group), and 3 cycles of 5 min similar ischemia, followed by 5 min of reperfusion each (RIPC II group). All animals were followed for 24 hr after the ischemia (reperfusion period). The liver ischemia-reperfusion injury was assessed by examining specific serum biomarkers indicating the magnitude of metabolic injury from selective blood samples of the hepatic circulation. In particular, the following parameters were examined: C-reactive protein, interleukin 6, tumor necrosis factor a, ferritin, and L-arginine., Results: All parameters were affected in the IR group as compared to the sham group. Both RIPC groups developed a less serious change as compared to the IR group, in all examined parameters., Conclusions: In an animal study of splanchnic ischemia produced in a way to this produced during a supraceliac aortic aneurysm open repair, the remote ischemic preconditioning seemed to attenuate the effect of hepatic ischemia-reperfusion injury., Clinical Relevance: Remote ischemic preconditioning produced with short bouts of ischemia of the lower body by temporary clamping of the infrarenal aorta might be used as a means of decreasing the detrimental effects of hepatic ischemia-reperfusion injury after supraceliac aortic cross-clamping. This was found in a swine model of suprarenal AAA open repair by studying the variance of certain biological biomarkers in selective blood samples retrieved from the hepatic vein., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Adipose-derived stromal cells (ADSCs)-derived exosomes (ADSC-Exos) account for the proangiogenic potential of stem cell. This study aimed to investigate the effect of ADSC-derived exosomes (ADSC-Exos) on the survival in fat grafting., Methods: A nude mouse model of subcutaneous fat grafting was adopted. Hypoxic preconditioned ADSC-Exos and ADSC-Exos were injected around the grafted tissue. The fat graft sample was weighed and examined by hematoxylin and eosin (H&E) staining and immunohistochemistry. Laser Doppler flowmetry and CD31 immunofluorescence staining were used to analyze neovascularization., Results: ADSC-Exo and hypoxic ADSC-Exo groups had a significantly higher weight of fat graft and more perilipin-positive adipocytes than the control groups from 2 to 8 weeks after grafting, and the hypoxic ADSC-Exo group had better outcomes (all P < 0.05). H&E staining showed that ADSC-Exos attenuated infiltration of inflammatory cells around the fat grafts. Laser Doppler flowmetry showed that the two ADSC-Exo groups had better blood perfusion in the graft tissue than the control groups (all P < 0.05). Immunofluorescence demonstrated that the hypoxic ADSC-Exo group had significantly more CD31-positive cells than the ADSC-Exo group. In vitro study showed that hypoxic ADSC-Exos treatment significantly increased the migration (at 12 and 24 h) and in vitro capillary network formation (at 12 h) in the human umbilical vein endothelial cells (HUVECs) as compared with the ADSC-Exo group and control group (all P < 0.05)., Conclusions: Co-transplantation of ADSC-Exos can effectively promote the survival of graft, neovascularization and attenuated inflammation in the fat grafts. Hypoxia treatment can further enhance the beneficial effect of ADSC-Exos., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A mild non-lethal ischemic episode can induce resistance to a subsequent severe ischemic injury in the brain. This phenomenon is termed ischemic tolerance or ischemic preconditioning, and is an endogenous mechanism that can provide robust neuroprotection. Because of its neuroprotective effects against cerebral ischemia or stroke, ischemic tolerance has been widely studied. However, almost all studies have been performed from the viewpoint of neurons. Accumulating evidence suggests that glial cells have various roles in regulation of brain function, including modulation of synaptic transmission, neuronal excitation, and neuronal structure. In addition, astrocytes are closely related to homeostasis, stability of brain function, and protection of neurons. However, glial cells have received only limited attention with regard to ischemic tolerance. Cross-ischemic preconditioning is a phenomenon whereby non-ischemic preconditioning such as mechanical, thermal, and chemical treatment can induce ischemic tolerance. Of these, chemical treatments that affect the immune system can strongly induce ischemic tolerance, suggesting that glial cells may have important roles in this process. Indeed, we and others have demonstrated that glial cells, especially astrocytes, play a pivotal role in the induction of ischemic tolerance. This glial-mediated ischemic tolerance provides a robust and long-lasting neuroprotection against ischemic injury. In this review, we discuss the mechanisms underlying glial-mediated ischemic tolerance, as well as its potential benefits, problems, and therapeutic application., (Copyright © 2017. Published by Elsevier B.V.)

Background: Isoflurane preconditioning (IPC) induces cerebral ischaemic tolerance, but the mechanism remains poorly understood. The aim of this study was to determine changes in mitochondrial function in the brain after IPC, and whether the cannabinoid receptor 1 (CB1R) could be involved in the mechanism of mitochondrial protection mediated by IPC., Methods: Adult male Sprague-Dawley rats were pretreated with isoflurane 2% for 1 h day -1 , for 5 days consecutively, and then subjected to 120 min right middle cerebral artery occlusion. Cannabinoid receptor 1 expression in the cellular and mitochondrial membrane was measured. The CB1R agonist HU-210 was administered alone, or the antagonists AM251 and SR141716A were given to the animals before each preconditioning. Neurological scores, infarct volume, apoptosis, and mitochondrial function were examined after middle cerebral artery occlusion., Results: Expression of CB1R on cellular and mitochondrial membranes was increased 6 h after preconditioning. Both IPC and HU-210 administration before middle cerebral artery occlusion improved neurological outcomes and reduced infarct volume. Isoflurane preconditioning increased the expression of the anti-apoptotic proteins Bcl-2 and Bcl-X L and reduced apoptosis in neurones. Isoflurane preconditioning and HU-210 also markedly preserved the activity of respiratory chain complexes, reduced mitochondrial radical generation, preserved mitochondrial membrane potential, and inhibited mitochondrial permeability transition pore opening. Cannabinoid receptor 1 antagonists abolished the improvement in mitochondrial function and the neuroprotective effects induced by IPC., Conclusions: Our results indicate that IPC elicits brain ischaemic tolerance and mitochondrial protection by activating the CB1R, which provides a new mechanism for IPC-induced neuroprotection against cerebral ischaemia., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Contrast-induced acute kidney injury (CI-AKI) is a common complication of many diagnostic and therapeutic cardiovascular procedures. It is associated with longer in-hospital stay, more complicated hospitalization course, and higher in-hospital morbidity and mortality. With increasing use of contrast media in various diagnostic and interventional procedures, the prevalence of CI-AKI is expected to rise. Although pre-hydration with intravenous normal saline is recommended in patients with elevated risk of CI-AKI, this approach is often not feasible in many clinical settings. Remote ischemic conditioning (RIC), elicited by application of one or more, brief, non-injurious episodes of ischemia and reperfusion of a limb, is a promising therapy for preventing or attenuating the deleterious effects of contrast media on the kidney. Although the mechanisms of protection by RIC have not been completely defined, complex humoral, neural, and inflammatory pathways have been hypothesized to be in play. Given that RIC is non-invasive and cheap, it is attractive from clinical and economic perspective as a therapy to protect the kidney from CI-AKI. In this succinct review, we highlight the unifying mechanisms of CI-AKI and provide an overview of proposed biological mechanisms of renal protection by RIC. Emerging pre-clinical and clinical evidence in interventional cardiology is also discussed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Acute kidney injury is a prevalent but underdiagnosed complication that is associated with increased in-hospital morbidity and mortality. The importance of this complication is being increasingly recognized. The lack of timely diagnostic methods and effective preemptive and therapeutic strategies make its perioperative management challenging. To reduce the incidence of acute kidney injury, it is crucial to focus the resources on high-risk patients who can be identified by clinical scoring systems with a high predictive value and newly developed renal biomarkers. The 'Kidney Disease: Improving Global Outcomes' guidelines recommend the implementation of preventive strategies that include a bundle of supportive measures. However, clear evidence to support such an approach is lacking. Previous studies demonstrated improved patients' outcome following remote ischemic preconditioning in high-risk patients. Other studies reached an opposite result. To date, renal replacement therapy is the "gold standard" for the treatment of severe acute kidney injury, although the ideal timing, technique, and application of this therapy remain under debate., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Ischaemia Reperfusion (IR) injury is a major cause of morbidity, mortality and graft loss following Orthotopic Liver Transplantation (OLT). Utilising marginal grafts, which are more susceptible to IR injury, makes this a key research goal. Remote Ischaemic Preconditioning (RIPC) has been shown to ameliorate hepatic IR injury in experimental models. Whether RIPC can reduce IR injury in human liver transplant recipients is unknown., Methods: Forty patients undergoing liver transplantation were randomized to RIPC or a sham. RIPC was induced through three 5 min cycles of alternate ischaemia and reperfusion of the left leg prior to surgery. Data on clinical outcomes was collected prospectively. Per-operative cytokine levels were measured., Results: Fourty five of 51 patients approached (88%) were willing to enroll in the study. Five patients were excluded and 40 randomized, of which 20 underwent RIPC which was successfully completed in all patients. There were no complications following RIPC. Median day 3 AST levels were slightly higher in the RIPC group (221 IU vs 149 IU, p = 1.00)., Conclusions: RIPC is acceptable and safe in liver transplant recipients. This study has not demonstrated evidence of a reduction in short-term measures of IR injury. Longer follow up will be required and consideration of an altered protocol., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Ischaemic preconditioning (IPC) phenomenon has been known for thirty years. During that time several studies showed that IPC provided by brief ischaemic and reperfusion episodes prior to longer ischaemia can bestow a protective effect to both preconditioned and also remote organs. IPC affecting remote organs is called remote ischaemic preconditioning. Initially, most IPC studies were focused on enhancing myocardial resistance to subsequent ischaemia and reperfusion injury. However, preconditioning was found to be a universal phenomenon and was observed in various organs and tissues including the heart, liver, brain, retina, kidney, skeletal muscles and intestine. Currently, there are a lot of simultaneous studies are underway aiming at finding out whether IPC can be helpful in protecting these organs. The mechanism of local and remote IPC is complex and not well known. Several triggers, intracellular pathways and effectors, humoral, neural and induced by genetic changes may be considered potential pathways in the protective activity of local and remote IPC. Local and remote IPC mechanism may potentially serve as heart protection during cardiac surgery and may limit the infarct size of the myocardium, can be a strategy for preventing the development of acute kidney injury development and liver damage during transplantation, may protect the brain against ischaemic injury. In addition, the method is safe, non-invasive, cheap and easily applicable. The main purpose of this review article is to present new advances which would help to understand the potential mechanism of IPC. It also discusses both its potential applications and utility in clinical settings., (Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Background: Ischemic preconditioning (IPC) is a strategy to reduce ischemia-reperfusion (I/R) injury. The protective effect of remote ischemic preconditioning (RIPC) on liver I/R injury is not clear. This study aimed to investigate the roles of RIPC in liver I/R in fatty liver rats and the involvement of endothelial nitric oxide synthase-nitric oxide (eNOS-NO) pathway and microRNA expressions in this process., Methods: A total of 32 fatty rats were randomly divided into the sham group, I/R group, RIPC group and RIPC+I/R group. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO) were measured. Hematoxylin-eosin staining was used to observe histological changes of liver tissues, TUNEL to detect hepatocyte apoptosis, and immunohistochemistry assay to detect heat shock protein 70 (HSP70) expression. Western blotting was used to detect liver inducible NOS (iNOS) and eNOS protein levels and real-time quantitative polymerase chain reaction to detect miR-34a, miR-122 and miR-27b expressions., Results: Compared with the sham and RIPC groups, serum ALT, AST and iNOS in liver tissue were significantly higher in other two groups, while serum NO and eNOS in liver tissue were lower, and varying degrees of edema, degeneration and inflammatory cell infiltration were found. Cell apoptosis number was slightly lower in the RIPC+I/R group than that in I/R group. Compared with the sham group, HSP70 expressions were significantly increased in other three groups (all P<0.05). Compared with the sham and RIPC groups, elevated miR-34a expressions were found in I/R and RIPC+I/R groups (P<0.05). MiR-122 and miR-27b were found significantly decreased in I/R and RIPC+I/R groups compared with the sham and RIPC groups (all P<0.05)., Conclusion: RIPC can reduce fatty liver I/R injury by affecting the eNOS-NO pathway and liver microRNA expressions., (Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.)

Background: Sevoflurane is one of the most commonly used volatile anesthetic agents with the fastest onset and offset, replacing isoflurane in modern anesthesiology. Preconditioning and postconditioning using volatile anesthetics can attenuate ischemia-reperfusion injury (IRI). However, no previous studies have evaluated the effect of sevoflurane in lung transplantation after cold ischemic injury. We aimed to study the effects of donor and recipient treatment with sevoflurane in a rat lung transplantation model., Methods: Lewis rats were allocated to four groups: control, PreC (preconditioning), PostC (postconditioning), and PreC + PostC. Donor rats in the PreC and PreC + PostC groups were exposed to 1.5% sevoflurane for 30 minutes before donor operation. Donor lungs were flushed with Perfadex and stored for 12 hours at 4°C before transplantation. Recipients received orthotopic left lung transplantation. In the PostC and PreC + PostC groups, sevoflurane was initiated 2 minutes before reperfusion and maintained for 30 minutes. Two hours after reperfusion, lung function was evaluated, and samples were collected for histologic, inflammatory, and cell death assessment., Results: Preconditioning and postconditioning using sevoflurane significantly improved the oxygenation of lung grafts (partial arterial gas pressure of oxygen: 198 mm Hg in control, 406.5 mm Hg in PreC, 472.4 mm Hg in PostC, and 409.7 mm Hg in PreC + PostC, p < 0.0001) and reduced pulmonary edema. Sevoflurane treatment reduced levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α. Moreover, sevoflurane significantly inhibited apoptotic cells by a decrease in cytochrome c release into cytosol and caspase-3 cleavage., Conclusions: Preconditioning or postconditioning of lungs using sevoflurane exhibits a significant protective effect against early phase of ischemia-reperfusion injury in a rat lung transplantation model., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Delayed graft function is a frequent complication following deceased donor renal transplantation, and is closely related to ischemia-reperfusion injury. Experimental and clinical studies have shown protection by remote ischemic conditioning (RIC). We hypothesized that recipient RIC before kidney graft reperfusion reduces the time to graft recovery. This multicenter, blinded, randomized, controlled clinical trial included 225 adult recipients of renal transplants from deceased donors at four transplantation centers in Denmark, Sweden, and the Netherlands. Participants were randomized 1:1 to RIC or sham-RIC. RIC consisted of 4 × 5-min thigh occlusion by an inflatable tourniquet each followed by 5-min deflation, performed during surgery prior to graft reperfusion. The tourniquet remained deflated for sham-RIC. The primary endpoint was the estimated time to a 50% decrease in baseline plasma creatinine (tCr50) calculated from plasma creatinine measurements 30 days posttransplant or 30 days after the last, posttransplant dialysis. No significant differences were observed between RIC and sham-RIC-treated patients in the primary outcome median tCr50 (122 h [95% confidence interval [CI] 98-151] vs. 112 h [95% CI 91-139], p = 0.58), or the number of patients receiving dialysis in the first posttransplant week (33% vs. 35%, p = 0.71). Recipient RIC does not reduce the time to graft recovery in kidney transplantation from deceased donors. ClinicalTrials.gov: NCT01395719., (© 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Remote ischemic preconditioning (RIPC) has been suggested to reduce postoperative release of cardiac and inflammatory markers in patients undergoing cardiac surgery. This study aimed to evaluate the effect of RIPC on nonischemic myocardial damage and inflammatory response in patients undergoing radiofrequency catheter ablation for paroxysmal atrial fibrillation (AF)., Methods: Seventy-two patients with drug-refractory paroxysmal AF undergoing radiofrequency catheter ablation were randomized into RIPC or control groups. RIPC (intermittent arm ischemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff) was performed once daily on 2 consecutive days before the ablation and immediately before ablation. Cardiac troponin-I (cTnI), high-sensitive C-reactive protein (hs-CRP), and interleukin (IL)-6 levels were measured before RIPC/sham RIPC, after the ablation, and 24 and 72h later. The early recurrence of atrial fibrillation (ERAF) in the two groups was observed over the subsequent 3months., Results: Radiofrequency ablation resulted in a significant rise in cTnI, hs-CRP, and IL-6 in both groups, which persisted for 72h. The RIPC group showed a lower increase in cTnI (P<0.001), hs-CRP (P=0.003), and IL-6 (P=0.008) than the control and tended to have a lower risk of ERAF (hazard ratio [HR]=0.77, 95% confidence interval [CI]: 0.32-1.88)., Conclusions: These results show that RIPC before ablation for paroxysmal AF significantly reduces the increase in cTnI, hs-CRP, and IL-6 associated with the procedure and results in a lower risk of ERAF. These findings suggest that RIPC could provide cardioprotection against nonischemic myocardial damage., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)