Remote Ischaemic Preconditioning Intervention Research Articles

Effect of remote ischemic preconditioning intervention on serum levels of microRNA-582–5p/HMGB1 in patients with acute cerebral infarction

ObjectiveAcute 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. MethodsIn 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. ResultsRIPC 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. ConclusionAfter 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.

Remote ischemic preconditioning enhances aerobic performance by accelerating regional oxygenation and improving cardiac function during acute hypobaric hypoxia exposure.

Remote ischemic preconditioning (RIPC) may improve exercise performance. However, the influence of RIPC on aerobic performance and underlying physiological mechanisms during hypobaric hypoxia (HH) exposure remains relatively uncertain. Here, we systematically evaluated the potential performance benefits and underlying mechanisms of RIPC during HH exposure. Seventy-nine healthy participants were randomly assigned to receive sham intervention or RIPC (4 × 5 min occlusion 180 mm Hg/reperfusion 0 mm Hg, bilaterally on the upper arms) for 8 consecutive days in phases 1 (24 participants) and phase 2 (55 participants). In the phases 1, we measured the change in maximal oxygen uptake capacity (VO2max) and muscle oxygenation (SmO2) on the leg during a graded exercise test. We also measured regional cerebral oxygenation (rSO2) on the forehead. These measures and physiological variables, such as cardiovascular hemodynamic parameters and heart rate variability index, were used to evaluate the intervention effect of RIPC on the changes in bodily functions caused by HH exposure. In the phase 2, plasma protein mass spectrometry was then performed after RIPC intervention, and the results were further evaluated using ELISA tests to assess possible mechanisms. The results suggested that RIPC intervention improved VO2max (11.29%) and accelerated both the maximum (18.13%) and minimum (53%) values of SmO2 and rSO2 (6.88%) compared to sham intervention in hypobaric hypoxia exposure. Cardiovascular hemodynamic parameters (SV, SVRI, PPV% and SpMet%) and the heart rate variability index (Mean RR, Mean HR, RMSSD, pNN50, Lfnu, Hfnu, SD1, SD2/SD1, ApEn, SampEn, DFA1and DFA2) were evaluated. Protein sequence analysis showed 42 unregulated and six downregulated proteins in the plasma of the RIPC group compared to the sham group after HH exposure. Three proteins, thymosin β4 (Tβ4), heat shock protein-70 (HSP70), and heat shock protein-90 (HSP90), were significantly altered in the plasma of the RIPC group before and after HH exposure. Our data demonstrated that in acute HH exposure, RIPC mitigates the decline in VO2max and regional oxygenation, as well as physiological variables, such as cardiovascular hemodynamic parameters and the heart rate variability index, by influencing plasma Tβ4, HSP70, and HSP90. These data suggest that RIPC may be beneficial for acute HH exposure.

Effect of remote ischemic preconditioning on cerebral oxygen saturation in aneurysmal subarachnoid hemorrhage: Secondary analysis of a randomized controlled trial

Remote ischemic preconditioning (RIPC) can ameliorate cerebral vasospasm and delayed cerebral ischemia and improve neurological outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Monitoring of regional cerebral oxygen saturation (rScO2) during the critical phase after aSAH can help detect ischemia and assess the effect of RIPC intervention. We investigated the effect of RIPC on rScO2 in patients with aSAH. Our study was a single-center, prospective, parallel-group, randomized pilot trial. After approval by institutional ethics committee, consenting patients (n = 25) with aSAH presenting within 72 h of ictus and scheduled for surgical clipping of cerebral aneurysm were randomized 1:1 to true RIPC (inflation of upper extremity blood pressure cuff thrice to 30 mmHg above systolic blood pressure for 5 min) or sham RIPC (inflation of blood pressure cuff thrice to 30 mmHg for 5 min). In this secondary analysis, our outcome measures assessed by a blinded observer were incidence of cerebral oxygen desaturation (COD) during 7–10 days after ictus and Glasgow outcome scale extended (GOSE) at discharge. The incidence of COD (decrease in rScO2 > 20% from baseline) was lower in the RIPC group (15.4% versus 33.3%); p = 0.378. The absence of ipsilateral COD resulted in a higher mean GOSE (estimate 1.15, p = 0.015). The RIPC group had a higher mean GOSE compared to sham group (estimate 0.8, p = 0.027). This pilot trial demonstrated that RIPC has the potential to prevent COD in patients with aSAH. Larger trials with cerebral oxygenation as the primary outcome are needed to confirm our findings.

The Role of RIPC in Preventing Organ Damage, Inflammation, and Oxidative Stress during Lower Limb DSA: A Randomised Controlled Trial.

Objective Diagnostic digital subtraction angiography (DSA) and DSA with percutaneous transluminal angioplasty (DSA-PTA) are common procedures for diagnosing and treating symptomatic lower extremity arterial disease (LEAD). However, organ damage following DSA and DSA-PTA is often underrecognised and hence undiagnosed. To reduce the risk induced by invasive procedures in symptomatic LEAD patients, the method of remote ischemic preconditioning (RIPC) has been suggested. The aim of the current study was to assess the effect of RIPC intervention on the organ damage markers profile, oxidative stress, and inflammation biomarkers in LEAD patients undergoing DSA and DSA-PTA procedure. Methods The RIPC intervention was performed by inflating a standard blood pressure cuff on the patient's upper arm to 200 mmHg for 5 minutes four times with 5-minute perfusion between each cycle. The sham intervention was performed similarly, but the cuff was inflated to 20 mmHg. Changes in the cardiac and renal damage biomarkers' profile, oxidative stress, and inflammation biomarkers were recorded before and 24 hours after DSA or DSA-PTA. Results A total of 111 (RIPC 54, sham 57) patients with symptomatic LEAD scheduled for endovascular procedure were randomised, and 102 patients (RIPC 47, sham 55) completed the study protocol. RIPC significantly limited the increase of adiponectine levels after DSA and DSA-PTA, compared to sham intervention (p = 0.020), but CK-MB levels were markedly lower in the sham group (p = 0.047) after procedure. There was no significant difference between the RIPC and the sham group in mean changes in hs-troponin-T (p = 0.25), NT-proBNP (p = 0.24), creatinine (p = 0.76), eGFR (p = 0.61), urea (p = 0.95), beta-2-microglobuline (p = 0.34), or cystatine C (p = 0.24) levels. Conclusion In this controlled clinical study, RIPC failed to improve the profile of renal and cardiac biomarkers in patients with LEAD periprocedurally. RIPC significantly limits the rise in adiponectin levels and may influence the decrease of CK-MB levels 24 hours after endovascular procedure.

Remote ischemic preconditioning in a setting of electrical cardioversion of early onset persistent atrial fibrillation (RIP CAF trial): Rationale and study design

BackgroundThe 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. AimThe 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? MethodsThe 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. ConclusionPreviously 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.

Remote ischemic preconditioning does not influence lectin pathway protein levels in head and neck cancer patients undergoing surgery.

Cancer patients who undergo tumor removal, and reconstructive surgery by transfer of a free tissue flap, are at high risk of surgical site infection and ischemia-reperfusion injury. Complement activation through the lectin pathway (LP) may contribute to ischemia-reperfusion injury. Remote ischemic preconditioning (RIPC) is a recent experimental treatment targeting ischemia-reperfusion injury. The study aims were to investigate LP protein plasma levels in head and neck cancer patients compared with healthy individuals, to explore whether RIPC affects LP protein levels in head and neck cancer surgery, and finally to examine the association between postoperative LP protein levels and the risk of surgical site infection. Head and neck cancer patients (n = 60) undergoing tumor resection and reconstructive surgery were randomized 1:1 to RIPC or sham intervention administered intraoperatively. Blood samples were obtained preoperatively, 6 hours after RIPC/sham, and on the first postoperative day. LP protein plasma levels were measured utilizing time-resolved immunofluorometric assays. H-ficolin and M-ficolin levels were significantly increased in cancer patients compared with healthy individuals (both P ≤ 0.02). Conversely, mannan-binding lectin (MBL)-associated serine protease (MASP)-1, MASP-3, collectin liver-1 (CL-L1), and MBL-associated protein of 44 kilodalton (MAp44) levels were decreased in cancer patients compared with healthy individuals (all P ≤ 0.04). A significant reduction in all LP protein levels was observed after surgery (all P < 0.001); however, RIPC did not affect LP protein levels. No difference was demonstrated in postoperative LP protein levels between patients who developed surgical site infection and patients who did not (all P > 0.13). The LP was altered in head and neck cancer patients. LP protein levels were reduced after surgery, but intraoperative RIPC did not influence the LP. Postoperative LP protein levels were not associated with surgical site infection.

Remote Ischemic Preconditioning in Microsurgical Head and Neck Reconstruction: A Randomized Controlled Trial.

Background:The free flap failure rate is 5% in head and neck microsurgical reconstruction, and ischemia–reperfusion injury is an important mechanism behind this failure rate. Remote ischemic preconditioning (RIPC) is a recent intervention targeting ischemia–reperfusion injury. The aim of the present study was to investigate if RIPC improved clinical outcomes in microsurgical reconstruction.Methods:Head and neck cancer patients undergoing tumor resection and microsurgical reconstruction were included in a randomized controlled trial. Patients were randomized (1:1) to RIPC or sham intervention administered intraoperatively just before transfer of the free flap. RIPC was administered by four 5-minute periods of upper extremity occlusion and reperfusion. Clinical data were prospectively collected in the perioperative period and at follow-up on postoperative days 30 and 90. Intention-to-treat analysis was performed.Results:Sixty patients were randomized to RIPC (n = 30) or sham intervention (n = 30). All patients received allocated intervention. No patients were lost to follow up. At 30-day follow-up, flap failure occurred in 7% of RIPC patients (n = 2) and 3% of sham patients (n = 1) with the relative risk and 95% confidence interval 2.0 [0.2;20.9], P = 1.0. The rate of pedicle thrombosis was 10% (n = 3) in both groups with relative risk 1.0 [0.2;4.6], P = 1.0. The flap failure rate did not change at 90-day follow-up.Conclusions:RIPC is safe and feasible but does not affect clinical outcomes in head and neck cancer patients undergoing microsurgical reconstruction.

Effects of Remote Ischaemic Preconditioning on Arterial Stiffness in Patients Undergoing Lower Limb Angiographic Procedures: A Randomised Clinical Trial

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. In the RIPC intervention, the blood pressure cuff on the arm was inflated to 200mmHg or to 20mmHg above systolic pressure, and in the sham intervention to 20mmHg. 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 24h after DSA. 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 (-0.41m/s in RIPC and-0.27m/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 24h after DSA. 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.

Effect of remote ischemic preconditioning on hemostasis and fibrinolysis in head and neck cancer surgery: A randomized controlled trial.

IntroductionThe aim of this randomized controlled trial was to investigate if remote ischemic preconditioning (RIPC) reduced platelet aggregation and increased fibrinolysis in cancer patients undergoing surgery and thereby reduced the risk of thrombosis.Materials and methodsHead and neck cancer patients undergoing tumor resection and microsurgical reconstruction were randomized 1:1 to RIPC or sham intervention. RIPC was administered intraoperatively with an inflatable tourniquet by four cycles of 5-min upper extremity occlusion and 5-min reperfusion. The primary endpoint was collagen-induced platelet aggregation measured with Multiplate as area-under-the-curve on the first postoperative day. Secondary endpoints were markers of primary hemostasis, secondary hemostasis, and fibrinolysis. Clinical data on thromboembolic and bleeding complications were prospectively collected at 30-day follow-up. An intention-to-treat analysis was performed.ResultsSixty patients were randomized to RIPC (n = 30) or sham intervention (n = 30). No patients were lost to follow-up. The relative mean [95% confidence interval] collagen-induced platelet aggregation was 1.26 [1.11;1.40] in the RIPC group and 1.17 [1.07;1.27] in the sham group on the first postoperative day reported as ratios compared with baseline (P = 0.30). Median (interquartile range) 50% fibrin clot lysis time was 517 (417–660) sec in the RIPC group and 614 (468–779) sec in the sham group (P = 0.25). The postoperative pulmonary embolism rate did not differ between groups (P = 1.0).ConclusionsRIPC did not influence hemostasis and fibrinolysis in head and neck cancer patients undergoing surgery. RIPC did not reduce the rate of thromboembolic complications.

The Effects of Remote Ischemic Preconditioning on Cognitive Function and Exercise Hyperemia in Isocapnic Hypoxia

Impairments in neurological and skeletal muscle function can occur in conditions of decreased oxygen delivery and vascular dysfunction can exacerbate any impairments. Remote ischemic preconditioning (RIPC) has been used to improve vascular functioning during exercise and cognitive tasks, but this intervention has yet to be tested in hypoxic conditions. Here, we test the hypothesis that RIPC can attenuate the hypoxia‐induced decline in cognitive function and also impact forearm blood flow during hypoxic exercise. Healthy, young men and women participated in two counterbalanced experimental sessions, consisting of two trials of rhythmic dynamic handgrip exercise (4 min, 10% maximal voluntary contraction) followed by computerized cognitive testing, once in normoxia (21% inspired O2), and once in isocapnic hypoxia (target O2 saturation ~85% via pulse oximetry). The cognitive tests (CNS Vital Signs) measured composite memory, verbal memory, visual memory, and processing speed. During rest and handgrip exercise, forearm blood flow (FBF) responses were determined via Doppler ultrasound and muscle oxygenation was assessed using near infrared spectroscopy (Moxy). Systemic hemodynamics [heart rate (ECG) and non‐invasive beat‐to‐beat blood pressure (Finometer)] were collected throughout. One experimental session consisted of RIPC (4 × 5 min thigh cuff inflation; 200 mmHg) between the normoxic and hypoxic trials whereas the other was a sham (~10 mmHg cuff pressure) intervention. Percent change (%Δ) from normoxia to hypoxia was determined for cognitive test scores. Preliminary results (n=6, mean±sem) demonstrate modest hypoxia‐induced declines in composite, verbal, and visual memory (−8.6±4.4%, −11.2±6.6%, −5.2±3.8%) but not processing speed in sham conditions. The RIPC intervention had no consistent impact on these hypoxia‐induced changes. Exercise hyperemia was increased in hypoxia vs normoxia (177±12 vs 163±6 ml/min in hypoxia vs normoxia, respectively) and RIPC modestly increased exercise hyperemia in hypoxia (191±10 ml/min) but had little effect during normoxia (167±12 ml/min). We conclude that RIPC has a minimal effect on the impact of hypoxia on cognitive function and can augment hypoxic exercise hyperemia in young, healthy humans.Support or Funding InformationUniversity of Dayton University Honors Program, Berry Summer Thesis Institute (JNS)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Remote ischaemic preconditioning for coronary artery bypass grafting (with or without valve surgery).

Despite substantial improvements in myocardial preservation strategies, coronary artery bypass grafting (CABG) is still associated with severe complications. It has been reported that remote ischaemic preconditioning (RIPC) reduces reperfusion injury in people undergoing cardiac surgery and improves clinical outcome. However, there is a lack of synthesised information and a need to review the current evidence from randomised controlled trials (RCTs). To assess the benefits and harms of remote ischaemic preconditioning in people undergoing coronary artery bypass grafting, with or without valve surgery. In May 2016 we searched CENTRAL, MEDLINE, Embase and Web of Science. We also conducted a search of ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). We also checked reference lists of included studies. We did not apply any language restrictions. We included RCTs in which people scheduled for CABG (with or without valve surgery) were randomly assigned to receive RIPC or sham intervention before surgery. Two review authors independently assessed trials for inclusion, extracted data and checked them for accuracy. We calculated mean differences (MDs), standardised mean differences (SMDs) and risk ratios (RR) using a random-effects model. We assessed quality of the trial evidence for all primary outcomes using the GRADE methodology. We completed a 'Risk of bias' assessment for all studies and performed sensitivity analysis by excluding studies judged at high or unclear risk of bias for sequence generation, allocation concealment and incomplete outcome data. We contacted authors for missing data. Our primary endpoints were 1) composite endpoint (including all-cause mortality, non-fatal myocardial infarction or any new stroke, or both) assessed at 30 days after surgery, 2) cardiac troponin T (cTnT, ng/L) at 48 hours and 72 hours, and as area under the curve (AUC) 72 hours (µg/L) after surgery, and 3) cardiac troponin I (cTnI, ng/L) at 48 hours, 72 hours, and as area under the curve (AUC) 72 hours (µg/L) after surgery. We included 29 studies involving 5392 participants (mean age = 64 years, age range 23 to 86 years, 82% male). However, few studies contributed data to meta-analyses due to inconsistency in outcome definition and reporting. In general, risk of bias varied from low to high risk of bias across included studies, and insufficient detail was provided to inform judgement in several cases. The quality of the evidence of key outcomes ranged from moderate to low quality due to the presence of moderate or high statistical heterogeneity, imprecision of results or due to limitations in the design of individual studies.Compared with no RIPC, we found that RIPC has no treatment effect on the rate of the composite endpoint with RR 0.99 (95% confidence interval (CI) 0.78 to 1.25); 2 studies; 2463 participants; moderate-quality evidence. Participants randomised to RIPC showed an equivalent or better effect regarding the amount of cTnT release measured at 72 hours after surgery with SMD -0.32 (95% CI -0.65 to 0.00); 3 studies; 1120 participants; moderate-quality evidence; and expressed as AUC 72 hours with SMD -0.49 (95% CI -0.96 to -0.02); 3 studies; 830 participants; moderate-quality evidence. We found the same result in favour of RIPC for the cTnI release measured at 48 hours with SMD -0.21 (95% CI -0.40 to -0.02); 5 studies; 745 participants; moderate-quality evidence; and measured at 72 hours after surgery with SMD -0.37 (95% CI -0.59 to -0.15); 2 studies; 459 participants; moderate-quality evidence. All other primary outcomes showed no differences between groups (cTnT release measured at 48 hours with SMD -0.14, 95% CI -0.33 to 0.06; 4 studies; 1792 participants; low-quality evidence and cTnI release measured as AUC 72 hours with SMD -0.17, 95% CI -0.48 to 0.14; 2 studies; 159 participants; moderate-quality evidence).We also found no differences between groups for all-cause mortality after 30 days, non-fatal myocardial infarction after 30 days, any new stroke after 30 days, acute renal failure after 30 days, length of stay on the intensive care unit (days), any complications and adverse effects related to ischaemic preconditioning. We did not assess many patient-centred/salutogenic-focused outcomes. We found no evidence that RIPC has a treatment effect on clinical outcomes (measured as a composite endpoint including all-cause mortality, non-fatal myocardial infarction or any new stroke, or both, assessed at 30 days after surgery). There is moderate-quality evidence that RIPC has no treatment effect on the rate of the composite endpoint including all-cause mortality, non-fatal myocardial infarction or any new stroke assessed at 30 days after surgery, or both. We found moderate-quality evidence that RIPC reduces the cTnT release measured at 72 hours after surgery and expressed as AUC (72 hours). There is moderate-quality evidence that RIPC reduces the amount of cTnI release measured at 48 hours, and measured 72 hours after surgery. Adequately-designed studies, especially focusing on influencing factors, e.g. with regard to anaesthetic management, are encouraged and should systematically analyse the commonly used medications of people with cardiovascular diseases.

Cardiac Troponin T and I Release After a 30-km Run

Prolonged endurance-type exercise is associated with elevated cardiac troponin (cTn) levels in asymptomatic recreational athletes. It is unclear whether exercise-induced cTn release mirrors a physiological or pathological underlying process. The aim of this study was to provide a direct comparison of the release kinetics of high-sensitivity cTnI (hs-cTnI) and T (hs-cTnT) after endurance-type exercise. In addition, the effect of remote ischemic preconditioning (RIPC), a cardioprotective strategy that limits ischemia-reperfusion injury, was investigated in a randomized controlled crossover manner. Twenty-five healthy volunteers completed an outdoor 30-km running trial preceded by RIPC (4× 5 min 220mm Hg unilateral occlusion) or control intervention. hs-cTnT, hs-cTnI, and sensitive cTnI (s-cTnI) concentrations were examined before, immediately after, 2 and 5 hours after the trial. The completion of a 30-km run resulted in a significant increase in circulating cTn (time: all p <0.001), with maximum hs-cTnT, hs-cTnI, and s-cTnI levels of 47 ± 27, 69 ± 62, and 82 ± 64ng/L (mean ± SD), respectively. Maximum hs-cTnT concentrations were measured in 60% of the participants at 2 hours after exercise, compared with maximum hs-cTnI and s-cTnI concentrations at 5 hours in 84% and 80% of the participants. Application of an RIPC stimulus did not reduce exercise-induced cTn release (time× trial: all p >0.5). In conclusion, in contrast to acute myocardial infarction, maximum hs-cTnT levels after exercise precede maximum hs-cTnI levels. Distinct release kinetics of hs-cTnT and hs-cTnI and the absence of an effect of RIPC favors the concept that exercise-induced cTn release may be mechanistically distinct from cTn release in acute myocardial infarction.

Remote ischaemic preconditioning shortens QT intervals during exercise in healthy subjects

The protective action of remote ischaemic preconditioning (RIPC) has been demonstrated in the context of surgical interventions in cardiology. Application of RIPC to sports performance has been proposed, but its effect on the electrocardiogram (ECG) during exercise remains unknown. This exploratory study aims to measure the changes in ventricular repolarization observed during exercise following RIPC in healthy subjects. In an experimental randomized crossover study, 17 subjects underwent two bouts of constant load exercise tests at 75% and 115% of gas exchange threshold (GET). Prior to exercise, they were allocated to either control or RIPC intervention with four cycles of 5 min of ischaemia followed by 5 min of reperfusion. ECG was continuously recorded during the protocol. QT and RR intervals were measured every 30 s (on an average tracing of the preceding 10 s). Although the time course of RR intervals did not differ between the two interventions (p = .56 at 75% GET and p = .74 at 115% GET), a significant shortening of QT intervals (measured from Q onset to T end) was observed during exercise (mean ± standard deviation of RIPC vs. control: −32 ± 19 ms at 75% GET (p < .001) and −34 ± 12 ms at 115% GET (p < .001)) as well as during recovery (−21 ± 8 ms at 75% GET (p < .001) and −16 ± 11 ms at 115% GET (p < .001)). This effect was not present at rest. These RIPC-related changes were clearly identifiable on the QT–RR loops after hysteresis reduction. RIPC therefore induces heart rate-independent shortening of QT intervals that is revealed during exercise.

The Impact of Remote Ischemic Pre-Conditioning on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography and Angioplasty: A Double-Blind Randomized Clinical Trial.

Background and objectiveContrast-induced nephropathy (CIN) is an acute major complication following intravascular administration of iodinated contrast agents; however, the best approach for preventing CIN is not clear. Remote ischemic pre-conditioning (RIPC) is a new, non-pharmacological method that has been considered for the prevention of CIN following coronary angiography. This study assessed the effects of RIPC with four brief episodes of upper limb ischemia and reperfusion in the prevention of contrast-induced nephropathy (CIN) after coronary angiography and/or angioplasty.MethodsIn this double-blind randomized clinical trial, we enrolled 51 patients with chronic stable angina and non-ST elevation acute coronary syndrome (NSTE.ACS), and they underwent coronary angiography and/or angioplasty. Standard fluid therapy with normal saline was prescribed for all patients before and after the procedure. The patients were divided into two groups, i.e., a study group of patients who had undergone RIPC intervention and a control group of patients who had not undergone RIPC. One hour before the procedure, a sphygmomanometer cuff was placed around one arm and inflated up to 50 mmHg above the systolic pressure for five minutes; then, the cuff was deflated for another five minutes, and this cycle was repeated four times. The patients’ serum creatinine levels were measured at baseline and 48 hours after the procedure, and the incidence of CIN was calculated.ResultsTwenty-one males and 30 females were studied in two groups, i.e., an RIPC intervention group (n = 25) and a control group (n = 26) that were homogenous considering baseline characteristics. No significant difference was observed in the mean level of serum creatinine between the two groups at a post-intervention time of 48 hours (RICP: 1.74 ± 0.70 mg/dL vs. Control: 1.75 ± 0.87 mg/dL; P = 0.64). However, a lower incidence rate of CIN was observed 48 hours after the administration of the contrast medium in the RIPC group, but it was not statistically significant (RIPC: 23.1% vs. Control: 12.0%; P = 0.30).ConclusionIt seems that adequate fluid therapy is still the most effective strategy for preventing CIN and that RIPC might have additional protective effects in very high risk patients, such as those with severe renal insufficiency and heart failure.

Remote ischaemic preconditioning versus sham procedure for abdominal aortic aneurysm repair: an external feasibility randomized controlled trial.

BackgroundDespite advances in perioperative care, elective abdominal aorta aneurysm (AAA) repair carries significant morbidity and mortality. Remote ischaemic preconditioning (RIC) is a physiological phenomenon whereby a brief episode of ischaemia-reperfusion protects against a subsequent longer ischaemic insult. Trials in cardiovascular surgery have shown that RIC can protect patients’ organs during surgery. The aim of this study was to investigate whether RIC could be successfully introduced in elective AAA repair and to obtain the information needed to design a multi-centre RCT.MethodsConsecutive patients presenting for elective AAA repair, using an endovascular (EVAR) or open procedure, in a single large city hospital in the UK were assessed for trial eligibility. Patients who consented to participate were randomized to receive RIC (three cycles of 5 min ischaemia followed by 5 min reperfusion in the upper arm immediately before surgery) or a sham procedure. Patients were followed up for 6 months. We assessed eligibility and consent rates, the logistics of RIC implementation, randomization, blinding, data capture, patient and staff opinion, and variability and frequency of clinical outcome measures.ResultsBetween January 2010 and December 2012, 98 patients were referred for AAA repair, 93 were screened, 85 (91 %) were eligible, 70 were approached for participation and 69 consented to participate; 34 were randomized to RIC and 35 to the sham procedure. There was a greater than expected variation in the complexity of EVAR that impacted the outcomes. Acute kidney injury occurred in 28 (AKIN 1: 23 %; AKIN 2: 15 % and AKIN 3: 3 %) and 7 (10 %) had a perioperative myocardial infarction. Blinding was successful, and interviews with participants and staff indicated that the procedure was acceptable. There were no adverse events secondary to the intervention in the 6 months following the intervention.ConclusionsThis study provided essential information for the planning and design of a multi-centre RCT to assess effectiveness of RIC for improving clinical outcomes in elective AAA repair. Patient consent was high, and the RIC intervention was carried out with minimal disruption to clinical care. The allocation scheme for a definite trial should take into account both the surgical procedure and its complexity to avoid confounding the effect of the RIC, as was observed in this study.Trial registrationCurrent Controlled Trials ISRCTN19332276 (date of registration: 16 March 2012). The trial protocol is available from the corresponding author.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0899-3) contains supplementary material, which is available to authorized users.

The Effects Of Remote Ischemic Preconditioning On Anaerobic Cycling Tests.

BACKGROUND: Remote ischemic preconditioning (RIPC) provides a substantial benefit for heart protection during surgery. Recent literature on RIPC reveals the potential to benefit the enhancement of sports performance as well. The aim of this study is to investigate the effect of RIPC on anaerobic performance. METHODS: :Seventeen healthy participants who practice regular physical activity participated in the project (nine women and eight men, mean age 28 years + / - 8 years). The participants were randomly assigned to an RIPC intervention (four 5-minute cycles of ischemia reperfusion, followed by five minutes using a pressure cuff) or a SHAM intervention in a cross-over design. After the intervention, the participants were tested for alactic anaerobic performance (six seconds of effort) followed by a Wingate test (lactic system) on an electromagnetic cycle ergometer (Excalibur, Lode BV, Groningen, Netherlands). The following parameters were evaluated: average power, peak power, the scale of perceived exertion, fatigue index (W/s), peak power (W), time to reach peak power (s), minimum power (W), the average power-to-weight ratio (W/kg) and the maximum power-to-weight ratio (W/kg). RESULTS: :The peak power for the Wingate test is 794 W for RIPC and 777 W for the control group (p = 0.208). The average power is 529 W (RIPC) versus 520 W for controls (p = 0.079). Perceived effort for RIPC is 9/10 on the Borg scale versus 10/10 for the control group (p = 0.123). CONCLUSION: Remote ischemic preconditioning does not offer any significant benefits for anaerobic performance.

Can Anaerobic Performance Be Improved by Remote Ischemic Preconditioning?

Remote ischemic preconditioning (RIPC) provides a substantial benefit for heart protection during surgery. Recent literature on RIPC reveals the potential to benefit the enhancement of sports performance as well. The aim of this study was to investigate the effect of RIPC on anaerobic performance. Seventeen healthy participants who practice regular physical activity participated in the project (9 women and 8 men, mean age 28 ± 8 years). The participants were randomly assigned to an RIPC intervention (four 5-minute cycles of ischemia reperfusion, followed by 5 minutes using a pressure cuff) or a SHAM intervention in a crossover design. After the intervention, the participants were tested for alactic anaerobic performance (6 seconds of effort) followed by a Wingate test (lactic system) on an electromagnetic cycle ergometer. The following parameters were evaluated: average power, peak power, the scale of perceived exertion, fatigue index (in watt per second), peak power (in Watt), time to reach peak power (in seconds), minimum power (in Watt), the average power-to-weight ratio (in watt per kilogram), and the maximum power-to-weight ratio (in watt per kilogram). The peak power for the Wingate test is 794 W for RIPC and 777 W for the control group (p = 0.208). The average power is 529 W (RIPC) vs. 520 W for controls (p = 0.079). Perceived effort for RIPC is 9/10 on the Borg scale vs. 10/10 for the control group (p = 0.123). Remote ischemic preconditioning does not offer any significant benefits for anaerobic performance.

Abstract 174: Remote Ischemic Preconditioning Improves Digital Vascular Endothelial Function and Enhances Circulating Nitric Oxide Formation in Healthy Volunteers

Background: Remote ischemic preconditioning (RIPC) induced by brief episodes of ischemia of the limb protects against organ damage by ischemia-reperfusion. It has been reported that RIPC improves endothelial function of the forearm in normal subjects and patients with coronary artery disease. However, the digital vascular endothelial response to RIPC has not been determined in healthy volunteers. Methods: This study was performed to examine effect of RIPC on fingertip digital vascular endothelial function by using endothelial pulse amplitude tonometry (EndoPAT) device and alteration in circulating nitric oxide(NO) level in peripheral blood. Ten healthy adult subjects (5 men, 5 women, mean age 25.2 years) had 3 cycles of 5 min ischemia alternating with 5 min reperfusion of the forearm. Another 10 healthy volunteers (6 men, 4 women, mean age 26.2 years) were used as the control group of sham and the cuff was inflated for 3 times at 10 mmHg for 5 minutes with 5-minute intervals. Fingertip digital vascular endothelial function of the ipsilateral arm was measured prior to first ischemia, 3h and 6h after the last episode of ischemia. Blood samples were taken from the contralateral arm prior to first ischemia, 3h and 6h after the last episode of ischemia. Results: Fingertip digital vascular endothelial function was significantly increase in 3h and 6h after the last RIPC intervention compared with the baseline condition(p&lt;0.05). In parallel the RIPC stimulus increased circulating NO formation(p&lt;0.05). There is a close association between finger vascular endothelial function and NO formation(p&lt;0.05). Conclusion: The present findings demonstrate for the first time that transient RIPC contributes to improvement of digital vascular endothelial function and increase in circulating NO production in healthy volunteers. Our data provide a novel evidence to support that RIPC might gain even wider application not only in disease but also in health.

692 The effect of remote ischemic preconditioning in heart failure: A randomized controlled pilot study

Remote ischemic preconditioning (RIPC) induced by transient limb ischemia confers myocardial and multi-organ protection in a variety of ischemic settings. RIPC may also improve skeletal muscle and exercise performance during activities limited by tissue hypoxia. To date, the effect of RIPC in patients with heart failure has not been explored, and may be associated with improved exercise capacity in this population. We performed a randomized double blind crossover trial of RIPC (4 cycles of 5-minutes upper limb ischemia/5 minutes reperfusion) compared to low-pressure sham control in ambulatory heart failure patients undergoing cardiopulmonary exercise testing. Patients with left ventricular systolic dysfunction and NYHA class II-IV heart failure were recruited from a single center, and randomly allocated to either RIPC or sham intervention immediately prior to undergoing symptom-limited stationary bicycle exercise with respiratory gas analysis. Patients then crossed over and completed the alternate intervention prior to repeat testing during a separate visit. The primary outcome measure was peak VO2 for RIPC versus sham; secondary outcomes included exercise duration, workload achieved and VE/VCO2 slope. Twenty patients completed the study protocol with paired testing a median of 18 days (IQ range 16-28 days) apart. Overall, RIPC prior to cardiopulmonary exercise testing was not associated with improvements in peak VO2 in this population (15.6 +/− 4.2 mL/kg/min vs 15.3 +/− 4.6 mL/kg/min; P = 0.33, for sham and RIPC, respectively). With respect to the secondary outcomes, there was no observed benefit of RIPC on exercise duration, workload achieved, anaerobic threshold, or VE/CO2 slope (Table). Post-hoc exploratory analysis did not identify any baseline clinical characteristics associated with an improved exercise performance following the RIPC intervention.Tabled 1 In this pilot study of RIPC in ambulatory heart failure patients with left ventricular systolic dysfunction, RIPC was not associated with improvements in objective measures of exercise capacity. Mechanistic studies and larger trials are needed to definitively rule out a benefit of RIPC in this population.