Blood flow restriction as a post-exercise recovery strategy: A systematic review of the current status of the literature.

The aim of this study was to systematically review the current literature on blood flow restriction (BFR) as a post-exercise recovery strategy. Experimental studies investigating the effect of BFR on recovery after exercise were included. Only studies meeting the following inclusion criteria were selected: (a) studies investigating about BFR as a post-exercise recovery strategy in athletes and healthy individuals; (b) the full text being available in English; (c) experimental research study design. Studies that exclusively analyzed BFR as a recovery strategy during the exercise (e.g., recovery strategy between bouts of exercise) were excluded. A literature review was conducted on the PubMed, Cochrane, and Web of Science electronic databases up until May 7th, 2023. The main findings were that (i) 9 studies investigated passive BFR as a post-exercise recovery strategy, which shows a significant lack of research in both team and individual sports (especially in female populations), and only 2 studies used active BFR protocols; (ii) although a high quality range of studies was observed, there were methodological limitations such as BFR interventions that were usually conducted after fatiguing protocols or fitness tests, which may not represent the real exercise (e.g., a sprint session of 6 sets of 50 m may induce muscle damage but it does not represent the demands of a team sport like rugby or soccer); (iii) there is a lack of consistency in BFR protocols (e.g., number of cycles or duration of the occlusion-reperfusion periods) for recovery; (iv) some studies showed beneficial effects while others found no positive or detrimental effects of BFR as a post-exercise recovery strategy in comparison with the control/SHAM group. In conclusion, only 11 studies investigated BFR as a post-exercise recovery strategy and there is not any significant amount of evidence in team or individual sports (especially in female populations). BFR could be a potential post-exercise recovery strategy, but practitioners should use caution when applying this method of recovery for their athletes and clients. In addition, it would be of interest for high performance-related practitioners to have a better understanding of the benefits of BFR interventions combined with either active or passive forms of exercise as a post-exercise recovery strategy.

Remote ischemic conditioning prevents ischemic cerebrovascular events in children with moyamoya disease: a randomized controlled trial.

BACKGROUND: Moyamoya disease (MMD) is a significant cause of childhood stroke and transient ischemic attacks (TIAs). This study aimed to assess the safety and efficacy of remote ischemic conditioning (RIC) in children with MMD. METHODS: In a single-center pilot study, 46 MMD patients aged 4 to 14 years, with no history of reconstructive surgery, were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year. The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events (MACEs). Secondary outcomes included ischemic stroke, recurrent TIA, hemorrhagic stroke, revascularization rates, and clinical improvement assessed using the patient global impression of change (PGIC) scale during follow-up. RIC-related adverse events were also recorded, and cerebral hemodynamics were evaluated using transcranial Doppler. RESULTS: All 46 patients completed the final follow-up (23 each in the RIC and sham RIC groups). No severe adverse events associated with RIC were observed. Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment [log-rank test (Mantel-Cox), P = 0.021]. At 3-year follow-up, two (4.35%) patients had an ischemic stroke, four (8.70%) experienced TIAs, and two (4.35%) underwent revascularization as the qualifying MACEs. The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale (65.2% vs. 26.1%, P < 0.01). No statistical difference in cerebral hemodynamics post-treatment was observed. CONCLUSIONS: RIC is a safe and effective adjunct therapy for asymptomatic children with MMD. This was largely due to the reduced incidence of ischemic cerebrovascular events.

Identification of New, Translatable ProtectomiRs against Myocardial Ischemia/Reperfusion Injury and Oxidative Stress: The Role of MMP/Biglycan Signaling Pathways.

INTRODUCTION: Ischemic conditionings (ICon) were intensively investigated and several protective signaling pathways were identified. Previously, we have shown the role of matrix metalloproteinases (MMP) in myocardial ischemia/reperfusion injury (MIRI) and the cardioprotective role of biglycan (BGN), a small leucine-rich proteoglycan in vitro. Here, we hypothesized that cardiac MMP and BGN signaling are involved in the protective effects of ICon. METHODS: A reverse target-microRNA prediction was performed by using the miRNAtarget™ 2.0 software to identify human microRNAs with a possible regulatory effect on MMP and BGN, such as on related genes. To validate the identified 1289 miRNAs in the predicted network, we compared them to two cardioprotective miRNA omics datasets derived from pig and rat models of MIRI in the presence of ICons. RESULTS: Among the experimentally measured miRNAs, we found 100% sequence identity to human predicted regulatory miRNAs in the case of 37 porcine and 24 rat miRNAs. Upon further analysis, 42 miRNAs were identified as MIRI-associated miRNAs, from which 24 miRNAs were counter-regulated due to ICons. CONCLUSIONS: Our findings highlight 24 miRNAs that potentially regulate cardioprotective therapeutic targets associated with MMPs and BGN in a highly translatable porcine model of acute myocardial infarction.

Stroke-heart syndrome: current progress and future outlook.

Stroke can lead to cardiac complications such as arrhythmia, myocardial injury, and cardiac dysfunction, collectively termed stroke-heart syndrome (SHS). These cardiac alterations typically peak within 72 h of stroke onset and can have long-term effects on cardiac function. Post-stroke cardiac complications seriously affect prognosis and are the second most frequent cause of death in patients with stroke. Although traditional vascular risk factors contribute to SHS, other potential mechanisms indirectly induced by stroke have also been recognized. Accumulating clinical and experimental evidence has emphasized the role of central autonomic network disorders and inflammation as key pathophysiological mechanisms of SHS. Therefore, an assessment of post-stroke cardiac dysautonomia is necessary. Currently, the development of treatment strategies for SHS is a vital but challenging task. Identifying potential key mediators and signaling pathways of SHS is essential for developing therapeutic targets. Therapies targeting pathophysiological mechanisms may be promising. Remote ischemic conditioning exerts protective effects through humoral, nerve, and immune-inflammatory regulatory mechanisms, potentially preventing the development of SHS. In the future, well-designed trials are required to verify its clinical efficacy. This comprehensive review provides valuable insights for future research.

Nephroprotective Effect of Ferula assa-foetida Oleo Gum Resin on Type 2 Diabetic Rats.

OBJECTIVE: Diabetic nephropathy is one of the main causes of kidney failure in the end stage of diabetes worldwide. On the other hand, asafoetida is a gum whose hypoglycemic effects have been proven. The present study was conducted with the aim of using asafoetida to prevent diabetic nephropathy. METHODS: Diabetes was induced by a high-fat diet (60%) and streptozotocin injection (35 mg/kg) in rats. Diabetic rats were treated with an oral dose of 50 mg/kg of asafoetida for 8 weeks. At the end of the experiment, serum and urine parameters were examined. Antioxidant enzymes and lipid peroxidation levels in the kidney were also determined along with its histological examination. The expression levels of tumor necrosis factor-alpha and Transforming growth factor beta genes were also evaluated. RESULTS: Glucose, cholesterol, triglyceride, and HbA1c concentrations were significantly reduced in the asafoetida 50. On the other hand, in the treatment group, serum creatinine, urea, and albumin levels decreased and increased in urine. Antioxidant enzymes in the kidney improved significantly, and the expression of tumour necrosis factor-alpha and transforming growth factor-beta genes decreased. Histopathological examination also showed that necrosis, epithelial damage, and leukocyte infiltration increased in the diabetic and the treatment group. CONCLUSION: The result of biochemical analysis, enzymatic, and histological examinations showed that asafoetida may delay the progression of diabetic nephropathy due to the presence of anti-inflammatory and antioxidant activities.

A novel NIR-II albumin-escaping probe for cerebral arteries and perfusion imaging in stroke mice model.

In order to guide the formulation of post-stroke treatment strategy in time, it is necessary to have real-time feedback on collateral circulation and revascularization. Currently used near-infrared II (NIR-II) probes have inherent binding with endogenous albumin, resulting in significant background signals and uncontrollable pharmacokinetics. Therefore, the albumin-escaping properties of the new probe, IR-808AC, was designed, which achieved timely excretion and low background signal, enabling the short-term repeatable injection for visualization of cerebral vessels and perfusion. We further achieved continuous observation of changes in collateral vessels and perfusion during the 7-d period in middle cerebral artery occlusion mice using IR-808AC in vivo. Furthermore, using IR-808AC, we confirmed that remote ischemic conditioning could promote collateral vessels and perfusion. Finally, we evaluated the revascularization after thrombolysis on time in embolic stroke mice using IR-808AC. Overall, our study introduces a novel methodology for safe, non-invasive, and repeatable assessment of collateral circulation and revascularization in real-time that is crucial for the optimization of treatment strategies.

Remote ischemic conditioning may improve graft function following kidney transplantation: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Remote ischemic conditioning (RIC) has the potential to benefit graft function following kidney transplantation by reducing ischemia-reperfusion injury; however, the current clinical evidence is inconclusive. This meta-analysis with trial sequential analysis (TSA) aimed to determine whether RIC improves graft function after kidney transplantation. METHODS: A comprehensive search was conducted on PubMed, Cochrane Library, and EMBASE databases until June 20, 2023, to identify all randomized controlled trials that examined the impact of RIC on graft function after kidney transplantation. The primary outcome was the incidence of delayed graft function (DGF) post-kidney transplantation. The secondary outcomes included the incidence of acute rejection, graft loss, 3- and 12-month estimated glomerular filtration rates (eGFR), and the length of hospital stay. Subgroup analyses were conducted based on RIC procedures (preconditioning, perconditioning, or postconditioning), implementation sites (upper or lower extremity), and graft source (living or deceased donor). RESULTS: Our meta-analysis included eight trials involving 1038 patients. Compared with the control, RIC did not significantly reduce the incidence of DGF (8.8% vs. 15.3%; risk ratio = 0.76, 95% confidence interval [CI], 0.48-1.21, P = 0.25, I2 = 16%), and TSA results showed that the required information size was not reached. However, the RIC group had a significantly increased eGFR at 3 months after transplantation (mean difference = 2.74 ml/min/1.73 m2, 95% CI: 1.44-4.05 ml/min/1.73 m2, P < 0.0001, I2 = 0%), with a sufficient evidence suggested by TSA. The secondary outcomes were comparable between the other secondary outcomes. The treatment effect of RIC did not differ between the subgroup analyses. CONCLUSION: In this meta-analysis with trial sequential analysis, RIC did not lead to a significant reduction in the incidence of DGF after kidney transplantation. Nonetheless, RIC demonstrated a positive correlation with 3-month eGFR. Given the limited number of patients included in this study, well-designed clinical trials with large sample sizes are required to validate the renoprotective benefits of RIC. TRIAL REGISTRATION: This systematic review and meta-analysis was registered at the International Prospective Register of Systematic Reviews (Number CRD42023464447).

Remote Ischemic Conditioning to Reduce Perihematoma Edema in Patients with Intracerebral Hemorrhage (RICOCHET): A Randomized Control Trial.

Background: Early perihematomal edema (PHE) growth is associated with worse functional outcomes at 90 days. Remote Ischemic conditioning (RIC) may reduce perihematomal inflammation if applied early to patients with intracerebral hemorrhage (ICH). We hypothesize that early RIC, delivered for seven days in patients with spontaneous ICH, may reduce PHE growth. Methods: ICH patients presenting within 6 h of symptom onset and hematoma volume < 60 milliliters (mL) were randomized to an RIC + standard care or standard care (SC) group. The primary outcome measure was calculated edema extension distance (EED), with the cm assessed on day seven. Results: Sixty patients were randomized with a mean ± SD age of 57.5 ± 10.8 years, and twenty-two (36.7%) were female. The relative baseline median PHE were similar (RIC group 0.75 (0.5-0.9) mL vs. SC group 0.91 (0.5-1.2) mL, p = 0.30). The median EEDs at baseline were similar (RIC group 0.58 (0.3-0.8) cm vs. SC group 0.51 (0.3-0.8) cm, p = 0.76). There was no difference in the median day 7 EED (RIC group 1.1 (0.6-1.2) cm vs. SC group 1 (0.9-1.2) cm, p = 0.75). Conclusions: Early RIC therapy delivered daily for seven days was feasible. However, no decrease in EED was noted with the intervention.

Rationale and Design of the IMPROVE Trial: A Multicenter, Randomized, Controlled, Open-label, Blinded-endpoint Trial Assessing the Efficacy of Remote Ischemic Conditioning in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting.

INTRODUCTION: Despite the appearance of off-pump coronary artery bypass grafting (CABG), ischemia-reperfusion injury (IRI) in the perioperative period still arouses concerns of clinicians. Remote ischemic conditioning (RIC) is the process of repeated ischemia and reperfusion in the peripheral vessels, which is proven to reduce IRI in vital organs. However, the effect of RIC in patients undergoing off-pump CABG is still unclear. METHODS: This IMPROVE trial is a national, multicenter, randomized, controlled, open-label, blinded-endpoint clinical trial designed to assess whether RIC intervention can improve short-term prognosis of patients undergoing off-pump CABG. It plans to enroll 648 patients who will be randomly assigned into a RIC group or control group. Patients in the RIC group will receive four cycles of 5 min of pressurization (about 200 mmHg) and 5 min of rest in the 3 days before and 7 days after the surgery. PLANNED OUTCOMES: The primary outcome is the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) within the 3-month follow-up. MACCE is defined as all-cause death, myocardial infarction, stroke, and coronary revascularization surgery. CLINICAL TRIAL REGISTRATION: NCT06141525 (ClinicalTrials.gov).

Ischemic preconditioning increases spinal excitability and voluntary activation during maximal plantar flexion contractions in men.

The enigmatic benefits of acute limb ischemic preconditioning (IP) in enhancing muscle force and exercise performance have intrigued researchers. This study sought to unravel the underlying mechanisms, focusing on increased neural drive and the role of spinal excitability while excluding peripheral factors. Soleus Hoffmann (H)-reflex /M-wave recruitment curves and unpotentiated supramaximal responses were recorded before and after IP or a low-pressure control intervention. Subsequently, the twitch interpolation technique was applied during maximal voluntary contractions to assess conventional parameters of neural output. Following IP, there was an increase in both maximum normalized force and voluntary activation (VA) for the plantar flexor group, with negligible peripheral alterations. Greater benefits were observed in participants with lower VA levels. Despite greater H-reflex gains, soleus volitional (V)-wave and sEMG amplitudes remained unchanged. In conclusion, IP improves muscle force via enhanced neural drive to the muscles. This effect appears associated, at least in part, to reduced presynaptic inhibition and/or increased motoneuron excitability. Furthermore, the magnitude of the benefit is inversely proportional to the skeletal muscle's functional reserve, making it particularly noticeable in under-recruited muscles. These findings have implications for the strategic application of the IP procedure across diverse populations.

Duration of Remote Ischemic Conditioning and Outcome in Acute Ischemic Stroke.

BACKGROUND: Remote ischemic conditioning has been found to be effective in improving functional outcomes in acute ischemic stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to determine whether long-term remote ischemic conditioning duration after stroke onset is associated with better clinical outcomes in ischemic stroke. METHODS AND RESULTS: Patients from the full analysis set were included in this secondary analysis. The primary outcome was the proportion of patients with an excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. Among the 1776 patients, there were 55 patients in the 1 to 7 days remote ischemic conditioning group, 345 in the 8 to 10 days group, 412 in the 11 to 13 days group, 51 in the 14 to 16 days group, and 913 in the control group. Compared with the control group, a significantly higher proportion of excellent functional outcomes at 90 days was found in the 11 to 13 days remote ischemic conditioning group (adjusted absolute difference, 9.1% [95% CI, 3.7%-14.5%]; P =0.001), which was attenuated in the other groups (adjusted absolute difference in the 8-10 days group, 2.0% [95% CI, -4.0% to 8.0%]; P=0.51; adjusted absolute difference in the 14-16 days group, 7.4% [95% CI, -5.8% to 20.5%]; P=0.27), but compared to the control group, there was lower proportion of excellent functional outcomes in the 1 to 7 days group (adjusted absolute difference, -14.4% [95% CI, -27.8% to 0.0%]; P=0.05). CONCLUSIONS: Among patients with acute moderate ischemic stroke, a higher likelihood of excellent clinical outcome was found in patients with longer duration of remote ischemic conditioning.

Remote Ischemic Conditioning in Stroke Recovery.

Remote ischemic conditioning (RIC) is a therapeutic strategy to protect a vital organ like the brain from ischemic injury through brief and repeat cycles of ischemia and reperfusion in remote body parts such as arm or leg. RIC has been applied in different aspects of the stroke field and has shown promise. This narrative review will provide an overview of how to implement RIC in stroke patients, summarize the clinical evidence of RIC on stroke recovery, and discuss unresolved questions and future study directions.

Remote ischemic conditioning improves cerebral hemodynamics in symptomatic intracranial atherosclerosis: A PET/CT-guided randomized controlled study.

Patients with symptomatic intracranial arterial stenosis (sICAS) suffer embarrassed hemodynamic status and acute ischemic stroke (AIS) recurrence. We aimed to assess the efficacy of remote ischemic conditioning (RIC) on improving this status by evaluating cerebral blood flow (CBF) and cerebral glucose metabolism (CGM) via PET/CT. Adult patients with unilateral sICAS in middle cerebral artery and/or intracranial segment of internal carotid artery-related AIS or transient ischemic attack within 6 months prior to randomization were enrolled. Individuals who received intravenous thrombolysis or endovascular treatment, or sICAS caused by cardiac embolism, small vessel occlusion, or other determined causes were excluded. Twenty-three eligible patients were randomly assigned to standard medical treatment (SMT) (n = 10) or RIC group (n = 13). The RIC protocol consisted of 5 cycles, each for 5-min bilateral upper limb ischemia and 5-min reperfusion period, twice a day, with a total duration of 3 months. Ten healthy volunteers were enrolled as healthy control group. We tested CBF and CGM at the rest stage and the methazolamide-induced stress stage. All patients received PET/CT at baseline and three-month followup. Both CBF and CGM in ipsilateral hemisphere of sICAS patients were significantly decreased at the rest stage and the stress stage (p < .05), which were improved by three-month RIC (p < .05). The lesions decreased notably in RIC group compared to SMT group (p < .05). RIC ameliorated the hemodynamic status and glucose metabolism in regions at high risk of infarction, which might improve the resistance capacity towards ischemic load in sICAS patients.

Is There a Mitochondrial Protection via Remote Ischemic Conditioning in Settings of Anticancer Therapy Cardiotoxicity?

PURPOSE OF REVIEW: To provide an overview of (a) protective effects on mitochondria induced by remote ischemic conditioning (RIC) and (b) mitochondrial damage caused by anticancer therapy. We then discuss the available results of studies on mitochondrial protection via RIC in anticancer therapy-induced cardiotoxicity. RECENT FINDINGS: In three experimental studies in healthy mice and pigs, there was a RIC-mediated protection against anthracycline-induced cardiotoxicity and there was some evidence of improved mitochondrial function with RIC. The RIC-mediated protection was not confirmed in the two available studies in cancer patients. In adult cancer patients, RIC was associated with an adverse outcome. There are no data on mitochondrial function in cancer patients. Studies in tumor-bearing animals are needed to determine whether RIC does not interfere with the anticancer properties of the drugs and whether RIC actually improves mitochondrial function, ultimately resulting in improved cardiac function.

Targeting blood brain barrier-Remote ischemic conditioning alleviates cognitive impairment in female APP/PS1 rats.

AIMS: Alzheimer's disease (AD) is a significant global health concern, and it is crucial that we find effective methods to prevent or slow down AD progression. Recent studies have highlighted the essential role of blood vessels in clearing Aß, a protein that contributes to AD. Scientists are exploring blood biomarkers as a potential tool for future AD diagnosis. One promising method that may help prevent AD is remote ischemic conditioning (RIC). RIC involves using sub-lethal ischemic-reperfusion cycles on limbs. However, a comprehensive understanding of how RIC can prevent AD and its long-term effectiveness is still lacking. Further research is essential to fully comprehend the potential benefits of RIC in preventing AD. METHODS: Female wild-type (WT) and APP/PS1 transgenic rats, aged 12 months, underwent ovariectomy and were subsequently assigned to WT, APP/PS1, and APP/PS1 + RIC groups. RIC was conducted five times a week for 4 weeks. The rats' depressive and cognitive behaviors were evaluated using force swimming, open-field tests, novel objective recognition, elevated plus maze, and Barnes maze tests. Evaluation of the neurovascular unit (NVU), synapses, vasculature, astrocytes, and microglia was conducted using immunofluorescence staining (IF), Western blot (WB), and transmission electron microscopy (TEM). Additionally, the cerebro-vasculature was examined using micro-CT, and cerebral blood flow (CBF) was measured using Speckle Doppler. Blood-brain barrier (BBB) permeability was determined by measuring the Evans blue leakage. Finally, Aß levels in the rat frontal cortex were measured using WB, ELISA, or IF staining. RESULTS: RIC enhanced memory-related protein expression and rescued depressive-like behavior and cognitive decline in APP/PS1 transgenic rats. Additionally, the intervention protected NVU in the rat frontal cortex, as evidenced by (1) increased expression of TJ (tight junction) proteins, pericyte marker PDGFRß, and glucose transporter 1 (GLUT1), as well as decreased VCAM1; (2) mitigation of ultrastructure impairment in neuron, cerebral vascular, and astrocyte; (3) upregulation of A2 astrocyte phenotype markers and downregulation of A1 phenotype markers, indicating a shift toward a healthier phenotype. Correspondingly, RIC intervention alleviated neuroinflammation, as evidenced by the decreased Iba1 level, a microglia marker. Meanwhile, RIC intervention elevated CBF in frontal cortex of the rats. Notably, RIC intervention effectively suppressed Aß toxicity, as demonstrated by the enhancement of α-secretase and attenuation of ß-secretase (BACE1) and γ- secretase and Aß1-42 and Aß1-40 levels as well. CONCLUSION: Chronic RIC intervention exerts vascular and neuroprotective roles, suggesting that RIC could be a promising therapeutic strategy targeting the BBB and NVU during AD development.

Baseline neurologic deficit and efficacy of remote ischemic conditioning after acute ischemic stroke: A post hoc analysis of RICAMIS.

RICAMIS (ClinicalTrials.gov Identifier: NCT03740971) trial has demonstrated efficacy of remote ischemic conditioning (RIC) in acute ischemic stroke, but whether baseline NIHSS score can affect outcomes in stroke remains unclear. We conducted a post hoc analysis of RICAMIS to investigate the issue. Patients included in RICAMIS were divided into three groups based on baseline NIHSS score. The primary outcome was excellent functional outcome at 90 days, defined as mRS score of 0-1. Compared with patients receiving usual care, we investigated association of RIC effect with outcomes in each group and interaction between RIC effect and stroke severity. Among 1776 patients, 1255 were assigned into NIHSS score 6-8 group, 402 into NIHSS score 9-12 group, and 119 into NIHSS score 13-16 group. A higher proportion of primary outcome was found associated with RIC in NIHSS score 9-12 group (adjusted risk difference [RD], 14.6 â€‹%; 95 â€‹% CI, 5.0 â€‹%-24.2 â€‹%; P â€‹= â€‹0.003), but no significant association was found in NIHSS score 6-8 group (adjusted RD, 2.3 â€‹%; 95 â€‹% CI, -2.5 â€‹%-7.2 â€‹%; P â€‹= â€‹0.34), or in NIHSS score 13-16 group (adjusted RD, 9.7 â€‹%; 95 â€‹% CI, -7.5 â€‹%-26.9 â€‹%; P â€‹= â€‹0.27). There was a significant interaction between RIC effect and stroke severity when analysis was performed between NIHSS score 6-8 and 9-12 groups (P â€‹= â€‹0.04), but not between NIHSS score 9-12 and 13-16 groups (P â€‹= â€‹0.57). Current study firstly reported patients with NIHSS score 9-12 may get more benefit from RIC after stroke with respect to excellent functional outcome at 90 days.

Dyslipidemia and Efficacy of Remote Ischemic Conditioning in Acute Moderate Ischemic Stroke: A Post Hoc Analysis of the RICAMIS Study.

BACKGROUND: Ischemic conditioning-induced cardioprotection was attenuated by dyslipidemia in some animal and clinical studies, which is not investigated in patients with stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to investigate the association of dyslipidemia on admission with the efficacy of remote ischemic conditioning (RIC). METHODS AND RESULTS: In this analysis, eligible patients were divided into dyslipidemia and normal-lipid groups according to the levels of 4 blood lipid profiles (total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), which were further subdivided into RIC and control subgroups. We analyzed the differences in functional outcome between RIC and control subgroups in dyslipidemia and normal-lipid patients, respectively, and the interaction effects of RIC treatment with blood lipid levels were evaluated. Among 1776 patients from intention-to-treat analysis, 1419 patients with data of blood lipid profiles were included in the final analysis. A significantly higher proportion of modified Rankin Scale score 0 to 1 was identified in the RIC versus control subgroup across the normal-total cholesterol group (69.9% versus 63.5%; P=0.04), normal-triglycerides group (68.1% versus 60.5%; P=0.016), high-low-density lipoprotein cholesterol group (65.7% versus 57.7%; P=0.025), and normal-high-density lipoprotein cholesterol group (68.3% versus 60.5%; P=0.005). Similar statistical trends were found in the high-total cholesterol group (62.8% versus 55.5%; P=0.059), high-triglycerides group (67.8% versus 60.1%; P=0.099), normal-low-density lipoprotein cholesterol group (69.8% versus 63.7%; P=0.105), but no statistical significance was found in the low-high-density lipoprotein cholesterol group (63.4% versus 61%; P=0.705). Furthermore, no significant interaction effect of RIC intervention by blood lipid profiles was found. Similar results were obtained for lipids as continuous variables. CONCLUSIONS: Blood lipids on admission was not associated with the neuroprotective effect of RIC.

Remote ischemic conditioning reduces adverse events in patients with acute ischemic stroke complicating acute myocardial infarction: a randomized controlled trial.

BACKGROUND: Acute ischemic stroke (AIS) complicating an acute myocardial infarction (AMI) is not uncommon, but can severely worsen the clinical prognosis. This study aimed to investigate whether remote ischemic conditioning (RIC) could provide clinical benefits to patients with AIS complicating AMI. METHODS: Subjects with AIS complicating AMI were recruited in this double-blind, randomized, controlled trial; assigned to the RIC and sham groups; and respectively underwent twice daily RIC and sham RIC for 2 weeks. All subjects received standard medical therapy. The primary endpoint was the rate of major adverse cardiac and cerebrovascular events (MACCEs) within 3 months after enrollment. MACCEs comprise of death from all causes, unstable anginas, AMI, acute ischemic strokes, and transient ischemic attacks. RESULTS: Eighty subjects were randomly assigned; 37 patients in the RIC group and 40 patients in the sham-RIC group completed the 3-month follow-up and were included in the final analysis. Both RIC and sham RIC procedures were well tolerated. At 3-month follow-up, 11 subjects (29.7%) in the RIC group experienced MACCEs compared to 21 (52.5%) in the sham group (hazard ratio [HR], 0.396; 95% confidence interval, 0.187-0.838; adjusted p < 0.05). Six subjects (16.2%) in the RIC group had died at the 3-month follow up, significantly lower than the 15 (37.5%) deaths in the sham group (adjusted HR 0.333; 95% CI 0.126-0.881; p = 0.027). Seventeen subjects (45.9%) in the RIC group and 6 subjects (15.0%) in the sham group achieved functional independence (mRS score ≤ 2) at 3-month follow-up (adjusted OR 12.75; 95% CI 2.104-77.21; p = 0.006). CONCLUSIONS: Among patients with acute ischemic stroke complicating acute myocardial infarction, treatment with remote ischemic conditioning decreased the major adverse cardiac and cerebrovascular events and improved functional outcomes at 90 days. TRIAL REGISTRATION: URL: www. CLINICALTRIALS: gov . Unique identifier: NCT03868007. Registered 8 March 2019.

Remote Ischemic Conditioning Mediates Cardio-protection After Myocardial Ischemia/Reperfusion Injury by Reducing 4-HNE Levels and Regulating Autophagy via the ALDH2/SIRT3/HIF1α Signaling Pathway.

Remote ischemic conditioning (RIC) can be effectively applied for cardio-protection. Here, to clarify whether RIC exerts myocardial protection via aldehyde dehydrogenase 2 (ALDH2), we established a myocardial ischemia/reperfusion (I/R) model in C57BL/6 and ALDH2 knockout (ALDH2-KO) mice and treated them with RIC. Echocardiography and single-cell contraction experiments showed that RIC significantly improved myocardial function and alleviated I/R injury in C57BL/6 mice but did not exhibit its cardioprotective effects in ALDH2-KO mice. TUNEL, Evan's blue/triphenyl tetrazolium chloride, and reactive oxygen species (ROS) assays showed that RIC's effect on reducing myocardial cell apoptosis, myocardial infarction area, and ROS levels was insignificant in ALDH2-KO mice. Our results showed that RIC could increase ALDH2 protein levels, activate sirtuin 3 (SIRT3)/hypoxia-inducible factor 1-alpha (HIF1α), inhibit autophagy, and exert myocardial protection. This study revealed that RIC could exert myocardial protection via the ALDH2/SIRT3/HIF1α signaling pathway by reducing 4-HNE secretion.

Remote ischemic conditioning for stroke: A critical systematic review.

Remote ischemic conditioning (RIC) is the application of brief periods of ischemia to an organ or tissue with the aim of inducing protection from ischemia in a distant organ. It was first developed as a cardioprotective strategy but has been increasingly investigated as a neuroprotective intervention. The mechanisms by which RIC achieves neuroprotection are incompletely understood. Preclinical studies focus on the hypothesis that RIC can protect the brain from ischemia reperfusion (IR) injury following the restoration of blood flow after occlusion of a large cerebral artery. However, increasingly, a role of chronic RIC (CRIC) is being investigated as a means of promoting recovery following an ischemic insult to the brain. The recent publication of two large, randomized control trials has provided promise that RIC could improve functional outcomes after acute ischemic stroke, and that there may be a role for CRIC in the prevention of recurrent stroke. Although less developed, there is also proof-of-concept to suggest that RIC may be used to reduce vasospasm after subarachnoid hemorrhage or improve cognitive outcomes in vascular dementia. As a cheap, well-tolerated and almost universally applicable intervention, the motivation for investigating possible benefit of RIC in patients with cerebrovascular disease is great. In this review, we shall review the current evidence for RIC as applied to cerebrovascular disease.