Effects Of Remote Ischemic Conditioning Research Articles

Remote ischemic conditioning improves myocardial parameters and clinical outcomes during primary percutaneous coronary intervention: a meta-analysis of randomized controlled trials.

We conducted a systematic review and meta-analysis to evaluate the effects of remote ischemic conditioning on myocardial parameters and clinical outcomes in ST segment elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention. Ten eligible randomized controlled trials with 1006 STEMI patients were identified. Compared with controls, remote ischemic conditioning reduced the myocardial enzyme levels (standardized mean difference =-0.86; 95% CI: -1.44 to -0.28; P = 0.004; I2 = 94.5%), and increased the incidence of complete ST-segment resolution [odds ratio (OR) = 1.74; 95% CI: 1.09 to 2.77; P = 0.02; I2 = 47.9%]. Remote ischemic conditioning patients had a lower risk of all-cause mortality (OR = 0.27; 95% CI: 0.12 to 0.62; P = 0.002; I2 = 0.0%) and lower major adverse cardiovascular and cerebrovascular events rate (OR=0.45; 95% CI: 0.27 to 0.75; P = 0.002; I2 = 0.0%). Meta-analysis suggested that remote ischemic conditioning conferred cardioprotection by reducing myocardial enzymes and increasing the incidence of complete ST-segment resolution in patients after STEMI. As a result, clinical outcomes were improved in terms of mortality and incidence of major adverse cardiovascular and cerebrovascular events.

The Diameter of Retinal Vessels Is Affected by Transient Ischemia of the Arm in Normal Persons.

Remote ischemic conditioning (RIC) implies that transient ischemia in a limb can affect perfusion in a target organ elsewhere in the body. The changes in perfusion can be assumed to be paralleled by changes in the vessel diameters in the target organ. It remains to be elucidated whether the diameter of normal retinal vessels can be used as a marker of RIC in vivo. In 20 normal persons aged 20 to 31 years the Dynamic Vessel Analyzer (DVA) was used to measure the resting diameter and diameter changes during isometric exercise and flicker stimulation before, immediately after, and 1 hour after RIC induced by transient ischemia in the left arm. The baseline diameter of retinal venules was reduced nonsignificantly immediately after (P = 0.07) and significantly 1 hour after RIC (P = 0.009), whereas the baseline diameter of arterioles was unaffected by the intervention (P = 0.61). Arterial constriction induced by isometric exercise was significantly reduced immediately after RIC (P = 0.04), but not 1 hour after RIC (P = 0.99). None of the other diameter responses were affected by RIC (P = 0.22 for all comparisons). The diameter of retinal vessels might potentially be a marker of ischemic conditioning in the body in general. The effect of RIC on retinal vascular diseases where ischemia is a part of the pathogenesis should be investigated.

Effects of Remote Ischemic Conditioning Methods on Ischemia-Reperfusion Injury in Muscle Flaps: An Experimental Study in Rats.

BackgroundThe aim of this study was to investigate the effects of remote ischemic conditioning on ischemia-reperfusion injury in rat muscle flaps histopathologically and biochemically.MethodsThirty albino rats were divided into 5 groups. No procedure was performed in the rats in group 1, and only blood samples were taken. A gracilis muscle flap was elevated in all the other groups. Microclamps were applied to the vascular pedicle for 4 hours in order to achieve tissue ischemia. In group 2, no additional procedure was performed. In groups 3, 4, and 5, the right hind limb was used and 3 cycles of ischemia-reperfusion for 5 minutes each (total, 30 minutes) was applied with a latex tourniquet (remote ischemic conditioning). In group 3, this procedure was performed before flap elevation (remote ischemic preconditoning). In group 4, the procedure was performed 4 hours after flap ischemia (remote ischemic postconditioning). In group 5, the procedure was performed after the flap was elevated, during the muscle flap ischemia episode (remote ischemic perconditioning).ResultsThe histopathological damage score in all remote conditioning ischemia groups was lower than in the ischemic-reperfusion group. The lowest histopathological damage score was observed in group 5 (remote ischemic perconditioning).ConclusionsThe nitric oxide levels were higher in the blood samples obtained from the remote ischemic perconditioning group. This study showed the effectiveness of remote ischemic conditioning procedures and compared their usefulness for preventing ischemia-reperfusion injury in muscle flaps.

Remote ischemic conditioning for the prevention of contrast-induced acute kidney injury in patients undergoing intravascular contrast administration: a meta-analysis and trial sequential analysis of 16 randomized controlled trials.

ObjectiveWe conducted this meta-analysis to examine the effect of remote ischemic conditioning (RIC) on contrast-induced acute kidney injury (CI-AKI) in patients undergoing intravascular contrast administrationon.MethodsPubmed, Embase, and Cochrane Library were comprehensively searched to identify all eligible studies by 15th March, 2017. Risk ratio (RR) and weighted mean difference with the corresponding 95% confidence intervals (CI) were used to examine the treatment effect. The heterogeneity and statistical significance were assessed with Q-test and Z-test, respectively.ResultsA total of 16 RCTs including 2175 patients were eventually analyzed. Compared with the control group, RIC could significantly decrease the incidence of CI-AKI (RR=0.58; 95% CI: 0.46, 0.74; P < 0.001), which was further confirmed by the trial sequential analysis. Subgroup analyses showed that remote ischemic preconditioning (RIPrC) and remote ischemic postconditioning (RIPoC) were both obviously effective, and perioperative hydration might enhance the efficiency of RIC. RIC also significantly reduced the major adverse cardiovascular events within six months.ConclusionRIC, whether RIPrC or RIPoC, could effectively exert renoprotective role in intravascular contrast administration and reduce the incidence of relevant adverse events.

Effects of Remote Ischaemic Conditioning on Heart Rate Variability and Cardiac Function in Patients With Mild Ischaemic Heart Failure

Cardioprotective effects of remote ischaemic conditioning (RIC) in the setting of ischaemic heart disease have been shown recently. But the effects of RIC on heart rate variability (HRV) and cardiac function in patients with stable ischaemic heart failure (IHF) are still unknown. Fifty patients with stable IHF were enrolled and randomly divided into RIC group and control group. Remote ischaemic conditioning treatment was performed twice a day for 6 weeks. A remote is chaemic conditioning protocol consisted of 4×5min inflation/deflation of the blood pressure cuff applied in the upper arm to create intermittent arm ischaemia. B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), 24-hour ambulatory electrocardiogram, and 6-minute walk distance (6MWD) were all assessed in two groups. Forty-seven patients completed the study. Remote ischaemic conditioning was well-tolerated by patients in the RIC group after 6 weeks treatment and LVEF showed a significant increase, from 39.2% to 43.4% (p<0.001), as well as decreased BNP, increased 6MWD and HRV, but this was not observed in the control group. In addition, the patients treated with RIC also showed improved NYHA class, LVEF, 6MWD, BNP level and HRV compared to control group. This study suggests that a 6-week course of RIC treatment could improve cardiac function and HRV in patients with mild and stable IHF, supporting widespread use of RIC in the daily lives of these patients.

Remote Ischemic Conditioning for Patients With STEMI.

ST-segment elevation myocardial infarction (STEMI) remains a leading cause of death and morbidity, despite declining incidence and improved short-term outcome in many countries. Although mortality declines in developed countries with easy and fast access to optimized treatment, development of heart failure often remains a challenge in survivors and still approaches 10% at 1 year. Rapid admission and acute interventional treatment combined with modern antithrombotic pharmacologic therapy frequently establish complete reperfusion and acutely stabilize the patient, but the reperfusion itself adds further to the damage in the myocardium compromising the long-term outcome. Reperfusion injury is believed to be a significant-if not the dominant-contributor to the net injury resulting from STEMI and has become a major focus of research in recent years. Despite a plethora of pharmacological and mechanical interventions showing consistent reduction of reperfusion injury in experimental models, translation into a clinical setting has been challenging. In patients, attempts to modify reperfusion injury by pharmacological strategies have largely been unsuccessful, and focus is increasingly directed toward mechanical modalities. Remote ischemic conditioning of the heart is achieved by repeated brief interruption of the blood supply to a distant part of the body, most frequently the arm. At present, remote ischemic conditioning is the most promising adjuvant therapy to reduce reperfusion injury in patients with STEMI. In this review, we discuss the results of clinical trials investigating the effect of remote ischemic conditioning in patients admitted with STEMI and potential reasons for its apparent superiority to current pharmacologic adjuvant therapies.

Meta-analysis of remote ischemic conditioning in patients with acute myocardial infarction

Effects of remote ischemic conditioning (RIC) in acute myocardial infarction (AMI) patients remain conflicting. We performed this meta-analysis of randomized clinical trials (RCTs) to evaluate the benefits of the RIC in patients with AMI. Potentially relevant RCTs were identified by searching PubMed, Embase, Cochrane Library, VIP, CNKI, and Wanfang database until November 2016. RCTs evaluating RIC using intermittent limb ischemia-reperfusion in AMI patients were included. Thirteen RCTs were identified and analyzed. Meta-analysis showed that RIC significantly reduced the area under the curve (AUC) of creatine kinase-myocardial band (CK-MB) (standardized mean difference [SMD] −0.29; 95% confidence intervals [CI] −0.44 to −0.14; P = 0.0002) and AUC of troponin T (SMD −0.22; 95% CI −0.37 to −0.08; P = 0.003). Risk ratio (RR) for ≥70% ST-segment resolution favored RIC group than the control group (RR 1.39; 95% CI 1.03–1.86; P = 0.03). RIC also significantly reduced all-cause mortality (RR 0.33; 95%CI 0.17–0.64; P = 0.001). Subgroup analyses on the CK-MB AUC and ST-segment resolution ≥70% rate showed that the effects of RIC appeared to be affected by the limb used, duration of RIC, and clinical setting. RIC may offer cardioprotective effects by improving ST-segment resolution and reducing the infarct size in AMI patients.

The effects of remote ischemic conditioning in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: a meta-analysis.

Timely and successful reperfusion is effective at improving outcome in patients presenting with ST elevation myocardial infarction (STEMI). However, abrupt restoration of blood flow may cause detrimental myocardial reperfusion injury. Remote ischemic conditioning (RIC) is a potent activator of innate protection against ischemia-reperfusion injury. This study assessed remote ischemic conditioning in patients presenting with STEMI treated with primary percutaneous coronary intervention (PCI). Relevant studies were identified through electronic literature search from PubMed, Medline, EMBASE, CNKI, WANFANG, and VIP. Studies published up to December 2015 were eligible for inclusion. RIC was performed by applying consecutive cycles of reocclusion/reperfusion through intermittent upper or lower limb ischemia before, during, or after reperfusion. The outcomes included creatine kinase-MB (CK-MB), ST resolution (STR), and left ventricular ejection fraction (LVEF). The 9 trials allocated 540 patients to perform RIC cycles before, during, or after reperfusion and 533 patients to usual PCI. Statistical analysis indicated that the peak of CK-MB and CK-MB AUC in RIC groups decrease significantly during the first 72 hours after PCI compared with controls (P=0.02 and P<0.01). The STR was significantly improved in RIC patients than in control subjects (P<0.001). LVEF is also improved 7 days after myocardial infarction (P=0.001). However, LVEF was not significantly different between study groups over 1 month (P=0.65). There may be a cardioprotective effect of RIC before, during, or after reperfusion, in the setting of acute STEMI.

Remote ischemic preconditioning in cardiac anesthesia: a review focusing on translation.

Remote ischemic conditioning (RIC) is a powerful cardioprotective strategy. Its clinical application is simple, cheap and so far free from secondary side effects. Given the heterogeneous results of recent large-scale clinical trials, its clinical relevant benefit is still doubted. Following a MEDLINE-based search on all publications concerning RIC in experimental or clinical settings, this review focuses on the translation from bench to bedside. A short resume of mechanistic insights is followed by the presentation of current clinical evidence of beneficial effects of RIC and the critical assessment of the recently published large-scale trials. Strong experimental evidence suggests beneficial cardioprotective effects induced by RIC. The signal transmission is sought to be achieved by a combination of neuronal and humoral signaling pathways. The protective effects of RIC are not limited to the heart alone: kidney, brain, gut, liver and lung have been experimentally shown to benefit from RIC. Thirty-two randomized clinical trials (N.=5409 cardiac patients) with cardiac surgery patients were published in the last decade. Their results are as heterogeneous as their monitored outcome parameters or strategies to apply RIC. The impressive experimental and clinical evidence in favor of RIC is opposed by the neutral results of the latest large-scale trials. While the underlying reasons for these neutral results are matter of on-going debate and could not be answered by recent published sub-investigations, additional adequately designed studies are encouraged by the mentioned results of experimental and pilot studies to exclude any confounding factors.

LO076: Remote ischemic conditioning to reduce reperfusion injury during acute STEMI: a systematic review and meta-analysis

Introduction: Remote ischemic conditioning (RIC) is a non-invasive therapeutic strategy that uses brief cycles of inflation and deflation of a blood pressure cuff to reduce ischemia-reperfusion injury during acute ST-elevation myocardial infarction (STEMI). The primary objective of this systematic review was to determine if RIC initiated prior to catheterization increases myocardial salvage index, defined as the proportion of area at risk of the left ventricle salvaged by treatment following emergent percutaneous coronary intervention (PCI) for STEMI. Secondary outcomes included infarct size and major adverse cardiovascular events. Methods: Electronic searches of PubMed, Ovid MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were conducted and reference lists were hand-searched. Randomized controlled trials comparing PCI with and without RIC for patients with STEMI published in English were included. Two reviewers independently screened abstracts, assessed quality of the studies, and extracted data. Data were pooled using random-effects models and reported as risk ratios (RR) with 95% confidence intervals (CIs). Results: Nine RCTs were included with a combined total of 999 patients (RIC+PCI = 534, PCI = 465). The myocardial salvage index was higher in the RIC+PCI group at 3 and 30 days; mean difference 0.09 (95% CI: 0.04, 0.15) and 0.12 (95% CI: 0.03, 0.21), respectively. Infarct size was reduced in the RIC+PCI group at 3 and 30 days; mean difference -3.82 (95% CI: -8.15, 0.51) and -4.00 (95% CI: -7.07, -0.93), respectively. There was no statistical difference with respect to death and re-infarction, however there was a reduction in heart failure with RIC+PCI at 6 months; RR: 0.43 (95% CI: 0.19, 0.99). Conclusion: RIC is emerging as a promising adjunctive treatment to PCI for the prevention of reperfusion injury in STEMI patients. Ongoing, multicenter clinical trials will help elucidate the effect of RIC on clinical outcomes such a hospitalization, heart failure and mortality.

Effect of remote ischaemic conditioning on coagulation and fibrinolysis

IntroductionRemote ischaemic conditioning (RIC) reduces infarct size and may improve prognosis in patients with acute myocardial infarction. To explore the potential mechanisms, we investigated the effects of RIC on coagulation and fibrinolysis. MethodsInterventional crossover study including 30 healthy drug-naïve males. Participants were exposed to a sham intervention (visit 1) and to RIC (visit 2 and 3) induced by intermittent arm ischaemia through four cycles of 5-min inflation of a blood pressure cuff followed by 5-min deflation. Prior to visit 3, all participants received aspirin 75mg daily for seven days. Blood samples were obtained at baseline as well as 5 and 45min after intervention. Whole blood coagulation was assessed by thromboelastometry (ROTEM®) and thrombin generation. Fibrinolysis was evaluated by clot turbidity-lysis, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1). ResultsNo differences were found in clot initiation, clot propagation or clot strength evaluated by ROTEM® (all p-values≥0.98). During aspirin treatment, clot initiation and clot propagation decreased after RIC evaluated by ROTEM® EXTEM® clotting time (p=0.04) and ROTEM® EXTEM® maximum velocity (p=0.03). After sham and RIC, thrombin generation declined as evaluated by reduced endogenous thrombin potential (RIC: p=0.001) and peak (RIC: p=0.01). After RIC during aspirin treatment, changes in thrombin generation were inconsistent; increased peak (p=0.04) and time to peak (p<0.001) and a decrease in lag-time (p<0.001).Clot lysis time was prolonged both after sham and after RIC (p<0.001). After RIC, PAI-1 levels declined (p=0.03), but t-PA levels also declined after all interventions (p-values≤0.04).Conclusion.RIC did not have substantial effects on coagulation or fibrinolysis compared to sham. Overall, aspirin did not influence the results.

Remote ischemic conditioning for kidney protection: A meta-analysis

BackgroundResults from randomized controlled trials (RCTs) concerning kidney effect of remote ischemic conditioning (RIC) are inconsistent. MethodsWe searched for relevant studies in Medline, Embase, the Cochrane Library, Google Scholar and Chinese database (SinoMed), as well as relevant references from their inception to November 2015. We performed a systematic review and meta-analysis of all eligible RCTs of RIC with kidney events. ResultsWe included 37 RCTs from 2007 to 2015 involving 8168 patients. Pooled analyses of all RCTs showed RIC significantly reduced the incidence of investigator-defined acute kidney injury (AKI) compared with control groups (RR 0.84, 95% CI 0.73-0.96, P = .009) (I2 = 25%). However, the difference was not significant when only RIFLE (Risk, Injury, Failure, Loss, End Stage), AKIN (Acute Kidney Injury Network), or KDIGO (Kidney Disease Improving Global Outcomes) criteria were applied to the definition of AKI (RR 0.87, 95% CI 0.74-1.02, P = .08) (I2 = 22%). In subgroup analysis, RIC showed a significant benefit on reducing investigator-defined AKI in patients following percutaneous coronary intervention (RR 0.64, 95% CI 0.46-0.87), but not after cardiac surgery (RR 0.93, 95% CI 0.82-1.06). There was no difference for changes in the incidence of renal replacement therapy, estimated glomerular filtration rate or serum creatinine. ConclusionsRIC might be beneficial for the prevention of investigator-defined AKI; however, the effect is likely small. Moreover, due to lack of an effect on use of renal replacement therapy, estimated glomerular filtration rate, RIFLE, AKIN, or KDIGO–defined AKI, and serum creatinine, the evidence for RIC is not robust. Finally, recent large-scale RCTs of RIC focusing on patient-centered outcomes do not support the wider application of RIC.

Effect of Remote Ischaemic Conditioning in Oncology Patients Undergoing Chemotherapy: Rationale and Design of the ERIC-ONC Study--A Single-Center, Blinded, Randomized Controlled Trial.

ABSTRACTCancer survival continues to improve, and thus cardiovascular consequences of chemotherapy are increasingly important determinants of long‐term morbidity and mortality. Conventional strategies to protect the heart from chemotherapy have important hemodynamic or myelosuppressive side effects. Remote ischemic conditioning (RIC) using intermittent limb ischemia‐reperfusion reduces myocardial injury in the setting of percutaneous coronary intervention. Anthracycline cardiotoxicity and ischemia‐reperfusion injury share common biochemical pathways in cardiomyocytes. The potential for RIC as a novel treatment to reduce subclinical myocyte injury in chemotherapy has never been explored and will be investigated in the Effect of Remote Ischaemic Conditioning in Oncology (ERIC‐ONC) trial (clinicaltrials.gov NCT 02471885). The ERIC‐ONC trial is a single‐center, blinded, randomized, sham‐controlled study. We aim to recruit 128 adult oncology patients undergoing anthracycline‐based chemotherapy treatment, randomized in a 1:1 ratio into 2 groups: (1) sham procedure or (2) RIC, comprising 4, 5‐minute cycles of upper arm blood pressure cuff inflations and deflations, immediately before each cycle of chemotherapy. The primary outcome measure, defining cardiac injury, will be high‐sensitivity troponin‐T over 6 cycles of chemotherapy and 12 months follow‐up. Secondary outcome measures will include clinical, electrical, structural, and biochemical endpoints comprising major adverse cardiovascular clinical events, incidence of cardiac arrhythmia over 14 days at cycle 5/6, echocardiographic ventricular function, N‐terminal pro‐brain natriuretic peptide levels at 3 months follow‐up, and changes in mitochondrial DNA, micro‐RNA, and proteomics after chemotherapy. The ERIC‐ONC trial will determine the efficacy of RIC as a novel, noninvasive, nonpharmacological, low‐cost cardioprotectant in cancer patients undergoing anthracycline‐based chemotherapy.

The Effect of Remote Ischemic Conditioning and Glyceryl Trinitrate on Perioperative Myocardial Injury in Cardiac Bypass Surgery Patients: Rationale and Design of the ERIC-GTN Study.

Remote ischemic conditioning (RIC) using transient limb ischemia/reperfusion has been reported to reduce perioperative myocardial injury in patients undergoing coronary artery bypass grafting and/or valve surgery. The role of intravenous glyceryl trinitrate (GTN) therapy administered during cardiac surgery as a cardioprotective agent and whether it interferes with RIC cardioprotection is not clear and is investigated in the ERIC-GTN trial ( http://www.clinicaltrials.gov: NCT01864252). The ERIC-GTN trial is a single-site, double-blind, randomized, placebo-controlled study. Consenting adult patients (age > 18 years) undergoing elective coronary artery bypass grafting ± valve surgery with blood cardioplegia will be eligible for inclusion. Two hundred sixty patients will be randomized to 1 of 4 treatment groups following anesthetic induction: (1) RIC alone, a RIC protocol comprising three 5-minute cycles of simultaneous upper-arm and thigh cuff inflation/deflation followed by an intravenous (IV) placebo infusion; (2) GTN alone, a simulated sham RIC protocol followed by an IV GTN infusion; (3) RIC + GTN, a RIC protocol followed by an IV GTN infusion; and (4) neither RIC nor GTN, a sham RIC protocol followed by IV placebo infusion. The primary endpoint will be perioperative myocardial injury as quantified by the 72-hour area-under-the-curve serum high-sensitivity troponin T. The ERIC-GTN trial will determine whether intraoperative GTN therapy is cardioprotective during cardiac surgery and whether it affects RIC cardioprotection.

The protective effect of remote ischemic conditioning in a septic mice model

The protective effect of remote ischemic conditioning in a septic mice model

The Effect of Remote Ischemic Conditioning on Bubble Formation in a Decompression Sick Rat Model

IntroductionDecompression sickness (DCS) is a disabling and potentially lethal condition where bubbles nucleate from supersaturated tissues during rapid decompression. These bubbles may obstruct end arteries and thereby induce ischemia and subsequent necrosis. Remote ischemic conditioning (rIC) has been proven to attenuate ischemia‐reperfusion injuries in the brain, heart, and after kidney transplantations.ObjectiveTo evaluate if rIC is associated with reduced damage in rats subjected to DCS.Method41 female Wistar rats were randomly assigned to rIC prior to (pre‐rIC; n=10) or after (per‐rIC; n=20) pressurization. A group of sham‐dive rats (n=11) was used as control. All groups were pressurized to 6 ATA (45 min) with subsequent decompression (0.5 ATA/min). rIC was performed with a custom made tourniquet strapped around one hind leg, accomplished by a series repeated 4 times: 5 min of ischemia followed by 5 min of reperfusion. DCS was evaluated with microultrasound imaging of the pulmonary artery for 2 hrs 20 min after decompression. Two days after the experimental procedure the brains were removed and histologically examined with 2,3,5‐triphenyltetrazolium chloride (TTC) to evaluate size of brain infarcted areas.ResultsMicroultrasound imaging showed no significant change in formation of nucleated bubbles in both pre‐ and per‐rIC treated groups compared to the control group. Similarly, TTC‐staining of the brain did not seem to indicate any differences between the groups.ConclusionThe lack of reduced bubble formation and brain damage in pre‐ or per‐rIC groups indicate that the rIC procedure was insufficient to treat DCS. Future studies are required to reveal the systemic response of rIC and its possible use in DCS treatment.

No effect of remote ischaemic conditioning on inflammation in a porcine kidney transplantation model

Main problemDelayed graft function after kidney transplantation is associated with decreased graft survival and increased patient mortality but the pathogenesis is poorly understood. Remote ischaemic conditioning (rIC) may prevent delayed graft function by an anti-inflammatory effect. In a porcine model of transplantation from adults to children, we investigated the inflammatory response in the transplanted kidney and the effect of rIC. MethodsKidneys were recovered from brain dead donor pigs(63kg) and transplanted into two groups of recipient pigs(15kg) after 22h of cold ischaemia. Recipients were randomised to either: rIC (n=8) performed before the 10-h reperfusion period or no-rIC (n=8). Non-transplanted kidneys from eight brain dead pigs served as controls. ResultsCompared to controls, transplantation increased the number of apoptotic cells, macrophages and neutrophils in the kidney. After transplantation, IL-10 levels increased and IL-6 levels decreased in the kidney, whereas levels of TNF-α and IL-8 were not affected. A significant rise in plasma IL-1β and IL-6 was observed in the recipients after transplantation. Plasma IL-10 was not affected by transplantation and TNF-α and IL-8 were below detection limit. No effect of rIC was found with regards to cell infiltration or cytokine production. ConclusionRenal transplantation elicits an inflammatory response in the kidney manifested as apoptotic cell death, macrophage and neutrophil infiltration, and an anti-inflammatory cytokine response 10h after transplantation. This response was not modified by rIC.

Effect of remote ischemic conditioning on systemic inflammatory response and survival rate in LPS-induced sepsis model

Hak, Choon L.; Kim, Y. H.; Yoo, H. N.; Lee, H. W.; Park, Y. C.; Kim, W. Y.; Kim, Yun Hee; Na Yoo, Hye; Won Lee, Hye; Park, Young Cheol; KIm, Woon Young Author Information

Safety, feasibility, and effect of remote ischemic conditioning in patients undergoing lung transplantation

Primary graft dysfunction (PGD) remains a significant problem after lung transplantation. Data from animal and clinical studies suggest that remote ischemic conditioning (RIC) may reduce ischemia-reperfusion injury in solid organ transplantation. A pilot randomized controlled trial of 60 patients undergoing bilateral sequential lung transplantation assessed the utility of RIC in attenuating PGD. Treated recipients underwent 3 cycles of lower limb ischemic conditioning before allograft reperfusion. The primary outcome measure was a comparison of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio) between treatment groups. No adverse effects of tourniquet application were observed. The mean lowest P/F ratio during the first 24 hours after transplantation was 271.3 mm Hg in the treatment arm vs 256.1 mm Hg in the control arm (p = 0.46). PGD grade and severity and the rate of acute rejection also showed a tendency to favor the treatment arm. Sub-group analysis demonstrated a significant benefit of treatment in patients with a primary diagnosis of restrictive lung disease, a group at high risk for the development of PGD. RIC was not accompanied by systemic release of high-molecular-weight group box 1. Levels of cytokines, high-molecular-weight group box 1, and endogenous secretory receptor for advanced glycation end products peaked within 2 hours after reperfusion and likely reflected donor organ quality rather than an effect of RIC. RIC did not significantly improve P/F ratios or PGD in this randomized controlled trial. However, encouraging results in this small study warrant a large multicenter trial of RIC in lung transplantation.

Protective effects of remote ischemic conditioning against ischemia/reperfusion-induced retinal injury in rats.

Limb remote ischemic conditioning (LRIC) provides a physiologic strategy for harnessing the body's endogenous protective capabilities against injury induced by ischemia-reperfusion in the central nervous system. The aim of the present study was to determine if LRIC played a role in protecting the retina from ischemia-reperfusion injury. A total of 81 adult male Sprague-Dawley rats were randomly assigned to sham and ischemia/reperfusion with or without remote LRIC arms. The retinal ischemic model was generated through right middle cerebral artery occlusion (MCAO) and pterygopalatine artery occlusion for 60 min followed by 1, 3, and 7 days of subsequent reperfusion. LRIC was conducted immediately following MCAO by tightening a tourniquet around the upper thigh and releasing for three cycles. Paraffin sections were stained with hematoxylin and eosin in order to quantify the number of cells in retinal ganglion cells (RGCs) layer throughout the duration of the study. Cellular expression of glial fibrillary acidic protein (GFAP) was detected and examined through immunohistochemistry. Protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was also analyzed by Western blot techniques. Our study demonstrated that the loss of cells in RGC layer was attenuated by LRIC treatment at 3 and 7 days following reperfusion (P < 0.05). Immunohistochemistry studies depicted a gradual increase (P < 0.05) in GFAP levels from day 1 through day 7 following ischemia and subsequent reperfusion, whereas LRIC reduced GFAP levels at 1, 3, and 7 days postreperfusion. In addition, LRIC increased the expression of Nrf2 and HO-1 at day 1 and 3 following ischemia/reperfusion. This particular study is the first remote conditioning study applicable to retinal ischemia. Our results strongly support the position that LRIC may be used as a noninvasive neuroprotective strategy, which provides retinal protection from ischemia-reperfusion injury through the upregulation of antioxidative stress proteins, such as Nrf2 and HO-1.