Remote Ischemic Conditioning Research Articles

Remote Ischemic Conditioning in Traumatic Brain Injury

Traumatic Brain Injury (TBI) is a major cause of disability, with no effective treatments for repetitive mild TBI (RmTBI). Remote Ischemic Conditioning (RIC) shows promise in stroke and may aid RmTBI recovery by reducing neuroinflammation. Using a mouse model, we found RIC significantly improved motor function post-RmTBI (p < 0.05), though anxiety and cognition remained unaffected. Ongoing studies will explore RIC’s effects on neuroinflammation and sex-based differences, highlighting its potential for clinical translation in RmTBI treatment.

Exploration of the Application of Remote Ischemic Conditioning in Nursing of Cardiac Arrest

Exploration of the Application of Remote Ischemic Conditioning in Nursing of Cardiac Arrest

Commentary on: Lipoprotein(a), remote ischemic conditioning, and stroke recurrence in patients with symptomatic intracranial atherosclerotic stenosis.

Commentary on: Lipoprotein(a), remote ischemic conditioning, and stroke recurrence in patients with symptomatic intracranial atherosclerotic stenosis.

Patients Receiving Remote Ischemic Conditioning in Early Stroke (PRICES) in the Philippines: An Open-Label Trial (P8-13.018)

Patients Receiving Remote Ischemic Conditioning in Early Stroke (PRICES) in the Philippines: An Open-Label Trial (P8-13.018)

Remote limb ischemic conditioning alleviates steatohepatitis via extracellular vesicle-mediated muscle-liver crosstalk.

Remote limb ischemic conditioning alleviates steatohepatitis via extracellular vesicle-mediated muscle-liver crosstalk.

Lipoprotein(a), remote ischemic conditioning, and stroke recurrence in patients with symptomatic intracranial atherosclerotic stenosis.

Lipoprotein(a), remote ischemic conditioning, and stroke recurrence in patients with symptomatic intracranial atherosclerotic stenosis.

Metabolic Syndrome and Efficacy of Remote Ischemic Postconditioning in Acute Moderate Ischemic Stroke: A Post Hoc Analysis of the RICAMIS Trial.

Metabolic syndrome (METS) is associated with poor outcomes after acute ischemic stroke. This study aimed to investigate the relationship between METS and efficacy of remote ischemic postconditioning (RIPostC) in acute moderate ischemic stroke using the database of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial. In the RICAMIS trial, eligible participants were patients with acute moderate ischemic stroke within 48 hours of onset who did not receive reperfusion treatment. A total of 1482 patients were enrolled in this secondary analysis, including the METS (602) and non-METS (880) group according to the METS definitions of the Chinese Diabetes Society, which was further subdivided into RIPostC and control subgroups. The primary outcome was excellent functional outcome, defined as a modified Rankin Scale score of 0 to 1 at 90 days. The differences in clinical outcomes between the RIPostC subgroup and control subgroup were compared in patients with METS or non-METS, respectively, and the interaction effects of RIPostC treatment assignment with METS status were evaluated. The baseline characteristics between RIPostC and control subgroups across patients with METS and non-METS were well balanced, except the difference in Trial of Org 10 172 in Acute Stroke Treatment stroke mechanism in the METS group. Compared with control, RIPostC was associated with high probability of excellent functional outcome in patients with METS (68.8% versus 56.1%; odds ratio [OR], 1.751 [95% CI, 1.248-2.456]; P=0.001), but not in patients without METS (66.6% versus 64.6%; OR, 1.103 [95% CI, 0.833-1.461]; P=0.494). Notably, a significant interaction effect between treatments (RIPostC or control) by different METS status on excellent functional outcome was observed (P=0.039). The secondary analysis suggests for the first time that RIPostC may provide greater benefit in patients with acute ischemic stroke with METS versus non-METS.

Remote ischemic conditioning: A bibliometric analysis

Abstract BACKGROUND: Remote ischemic conditioning (RIC) has gained significant attention across various professional fields as a safe and effective neuroregulatory technique. To gain a comprehensive understanding of the current status, emerging trends, and potential future directions in this field, a swift and intuitive statistical analysis method is essential for summarizing the available information. METHODS: This review conducted a literature search using the Web of Science Core Collection database and utilized VOSviewer software for visualization and analysis of publication trends, countries of origin, and keywords spanning the years 1985 to 2023. RESULTS: From 1998 to 2023, a total of 1,524 reviews on RIC were published, demonstrating a consistent increase in publications over the years. China emerged as the leading contributor in terms of publication, but the average number of citations was not dominant. Current RIC research hotspots encompass mechanism studies, stroke, neuroprotection, and cardiac protection. Among these, stroke, neuroprotection, and mechanisms play a major role in future. CONCLUSIONS: There is a consistent upward trajectory in RIC research publications. While China led in terms of publication quantity, the recognition of articles still needs to be improved. Stroke, neuroprotection, and mechanism research are poised to be the primary research focal points in the present and future of RIC studies.

Effect of Remote Ischemic Conditioning on the Form and Function of Red Blood Cells in Patients With Acute Ischemic Stroke.

Remote ischemic conditioning (RIC) is a simple and low-cost intervention that is thought to increase collateral blood flow through the vasodilatory effects of nitric oxide (NO) produced by the endothelium and red blood cells (RBCs). This study aims to investigate whether RIC affects RBC deformability and levels of NO and nitrite in patients with ischemic stroke. This is a predefined substudy to the RESIST (Remote Ischemic Conditioning in Patients With Acute Stroke Trial) randomized clinical trial conducted in Denmark. RIC was started in the ambulance and continued at the hospital for seven days. Blood samples were collected at different time points: prehospital in the ambulance, in-hospital upon arrival, 2 hours postadmission, and 24 hours postadmission. RBC deformability and erythrocyte aggregation rate were assessed using ektacytometry, NO using flowcytometry, and nitrite content using ozone chemiluminescence. Of 1500 prehospital randomized patients, 486 patients were included in this study between July 28, 2020, and November 11, 2023, and had blood samples taken. Of these, 249 (51%) had AIS, and here RIC treatment was not associated with increased RBC maximal deformability (RIC, 0.549; sham, 0.548; P=0.31), RBC NO (RIC, 35 301 median fluorescence intensity; sham, 34979 median fluorescence intensity; P=0.89), or nitrite (RIC, 0.036 µmol/L; sham, 0.034 µmol/L; P=0.38), but RIC treatment was associated with a significantly reduced aggregation pressure and a slower erythrocyte aggregation rate (RIC, 323.76 millipascal; sham, 352.74 millipascal; P=0.0113). Prehospital and in-hospital RIC significantly reduced erythrocyte aggregation rate in patients with acute ischemic stroke, while there was no change in RBC deformability, NO content, or whole blood nitrite levels. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481777.

Neuroprotective effects of remote ischemic conditioning in acute ischemic stroke: a meta-analysis

Stroke is one of the leading causes of death and disability worldwide, making the search for effective neuroprotective and neurorepair strategies crucial. Remote ischemic conditioning, as an endogenous neuroprotective method, involves transient limb ischemia followed by reperfusion, potentially reducing the infarct area and improving neurological function. Although animal studies have indicated the neuroprotective effects of remote ischemic conditioning, its clinical efficacy in patients with acute ischemic stroke remains controversial. This meta-analysis aims to evaluate the efficacy and safety of remote ischemic conditioning in patients with acute ischemic stroke, focusing on its effects on neurological recovery and neuroprotection. We performed a comprehensive search of the PubMed, Web of Science, Scopus, and Cochrane databases for randomized controlled trials published from their inception to 2023. Studies were included if they met the following criteria: 1) they were randomized controlled trials; 2) they involved patients with acute ischemic stroke or transient ischemic attack; and 3) they included adult patients with a baseline National Institutes of Health Stroke Scale score of less than 24 and a modified Rankin Scale score of 2 or lower. We excluded animal studies, review articles, and studies for which full texts were not accessible. The quality of the included studies was evaluated via the Cochrane Collaboration tool, and the data were analyzed with Cochrane Review Manager 5.3, utilizing either fixed-effect or random-effects models to evaluate heterogeneity. Ultimately, 11 randomized controlled trials involving 5407 patients (2682 in the remote ischemic conditioning group and 2725 in the control group) were included. The results revealed that remote ischemic conditioning significantly reduced the National Institutes of Health Stroke Scale score at 90 days (MD = –0.75, 95% CI: –1.48, –0.01, P = 0.05) and increased the rate of good functional outcomes (modified Rankin Scale score 0–1) (RR = 1.08, 95% CI: 1.12, 1.15, P = 0.01). Additionally, remote ischemic conditioning significantly decreased the recurrence rate of acute ischemic stroke (RR = 0.79, 95% CI: 0.78, 0.93; P = 0.0003). However, remote ischemic conditioning did not significantly affect the volume of brain infarction. These results suggest that remote ischemic conditioning has significant neuroprotective effects in patients with acute ischemic stroke, improving neurological recovery and reducing stroke recurrence rates. Although the effects on the volume of brain infarction are not significant, remote ischemic conditioning is a safe and straightforward treatment method that provides an effective neuroprotective strategy for patients with acute ischemic stroke, particularly for improving long-term neurological outcomes and preventing stroke recurrence. Future research should further explore the neuroprotective mechanisms of remote ischemic conditioning and optimize treatment protocols to promote nerve repair.

Effects of Remote Ischemic Conditioning on Postoperative Recovery After Hepatectomy: A Randomised Controlled Trial.

Remote ischemic conditioning (RIC) has shown promise in preclinical and clinical studies, but its effectiveness in reducing hepatic ischemia-reperfusion injuries (HIRIs) and enhancing postoperative recovery after hepatectomy remains uncertain. In this study, we aimed to evaluate the impact of perioperative RIC (PRIC) on postoperative recovery in patients undergoing hepatectomy. A randomised controlled trial was performed. A total of 135 eligible patients were randomised to either a control group (sham RIC), a PRIC-1 group (RIC once daily for 3 days starting on the day of surgery) or a PRIC-2 group (RIC twice daily). The primary outcome was the time to 2 times the upper limit of normal (2ULN) alanine transaminase (ALT) levels post-hepatectomy. Secondary outcomes included time to reach 2ULN for aspartate transaminase (AST) levels, the area under the concentration-time curve on postoperative Day 7 (AUC-POD7) for ALT, AST, total bilirubin and lactic acid, as well as assessments of gastrointestinal function and postoperative complications. Median time to 2ULN ALT was shorter in the PRIC-1 and PRIC-2 groups than in the control group (PRIC-1: 5.0 [3.5, 6.0] vs. control: 7.0 [7.0, 10.0] days, p < 0.001; PRIC-2: 5.0 [4.0, 8.0] vs. control: 7.0 [7.0, 10.0] days, p < 0.001). The AUC-POD7 for ALT and AST, time to 2ULN AST, time to gastrointestinal tolerance and postoperative complications were significantly improved in the PRIC groups compared with thecontrols. PRIC is safe and effective in reducing HIRIs and enhancing recovery post-hepatectomy. Once-daily PRIC offers similar benefits to twice-daily PRIC. NCT06130436 (ClinicalTrials.gov).

Corrigendum to “Remote ischemic conditioning in the treatment of acute cerebral infarction: A case control study” [Heliyon Volume 9, Issue 7, July 2023, Article e18181

Corrigendum to “Remote ischemic conditioning in the treatment of acute cerebral infarction: A case control study” [Heliyon Volume 9, Issue 7, July 2023, Article e18181

Ischemic Conditioning Promotes Transneuronal Survival and Stroke Recovery via CD36-Mediated Efferocytosis.

Remote ischemic conditioning (RIC) has been implicated in cross-organ protection in cerebrovascular disease, including stroke. However, the lack of a consensus protocol and controversy over the clinical therapeutic outcomes of RIC suggest an inadequate mechanistic understanding of RIC. The current study identifies RIC-induced molecular and cellular events in the blood, which enhance long-term functional recovery in experimental cerebral ischemia. Naive mice or mice subjected to transient ischemic stroke were randomly selected to receive sham conditioning or RIC in the hindlimb at 2 hours post-stroke. At 3 days post-stroke, monocyte composition in the blood was analyzed, and brain tissue was examined for monocyte-derived macrophage (Mφ), levels of efferocytosis, and CD36 expression. Mouse with a specific deletion of CD36 in monocytes/Mφs was used to establish the role of CD36 in RIC-mediated modulation of efferocytosis, transneuronal degeneration, and recovery following stroke. RIC applied 2 hours after stroke increased the entry of monocytes into the injured brain. In the postischemic brain, Mφ had increased levels of CD36 expression and efferocytosis. These changes in brain Mφ were derived from RIC-induced changes in circulating monocytes. In the blood, RIC increased CD36 expression in circulating monocytes and shifted monocytes to a proinflammatory Lymphocyte antigen 6 complex (LY6C)High state. Conditional deletion of CD36 in Mφ abrogated the RIC-induced monocyte shift in the blood and efferocytosis in the brain. During the recovery phase of stroke, RIC rescued the loss of the volume and of tyrosine hydroxylase+ neurons in substantia nigra and behavioral deficits in wild-type mice but not in mice with a specific deletion of CD36 in monocytes/Mφs. RIC induces a shift in monocytes to a proinflammatory state with elevated CD36 levels, and this is associated with CD36-dependent efferocytosis in Mφs that rescues delayed transneuronal degeneration in the postischemic brain and promotes stroke recovery. Together, these findings provide novel insight into our mechanistic understanding of how RIC improves poststroke recovery.

Effect of perioperative remote ischemic conditioning on myocardial injury in patients with unstable angina undergoing percutaneous coronary intervention: protocol of a multicenter, randomized, double-blind clinical trial

BackgroundCardiovascular disease is a leading cause of death, with ischemic heart disease being a significant contributor. While percutaneous coronary intervention (PCI) effectively reduces mortality in myocardial infarction patients, its efficacy for unstable angina (UA) patients is controversial. Complications associated with PCI further limit application in UA. RIC is hypothesized to be an effective co-intervention that reduces PCI-related complications and may potentially enhance the efficacy of the PCI procedure itself.MethodsThis is a pragmatic, prospective, dual-center, double-blind, randomized controlled clinical trial assessing the effect of remote ischemic conditioning (RIC) during percutaneous coronary intervention (PCI) on injury in unstable angina patients aged ≥ 18 years undergoing coronary angiography. Participants will be randomized to receive either RIC or Sham RIC, in addition to standard pharmacotherapy. Primary outcome includes periprocedural myocardial injury measured by hs-cTnT levels, while secondary outcomes encompass major adverse cardiovascular events, coronary artery lesions Gensini Score, arrhythmia, angina incidence, SAQ scores, ECG changes, and cardiac function assessed by two-dimensional echocardiography. The trial aims to recruit 574 participants and is scheduled to be initiated on 15 January 2024. We will conduct the primary statistical analysis using the intention-to-treat principle. Results from the trial will be presented as comparative summary statistics following the Consolidated Standards of Reporting Trials (CONSORT) guidelines.Trial registrationChiCTR2400079855, 15 January 2024.

Effect of RICAS (Remote Ischemic Preconditioning on Collaterals of Atherosclerosis Stroke): Rationale andDesign.

As a noninvasive, low-cost, nonpharmacological procedure with excellent properties of safety, remote ischemic conditioning (RIC) has been demonstrated to prevent recurrence of stroke among patients with ischemic stroke of large artery atherosclerosis origin. We hypothesized that the benefit is attributed to the improvement of collaterals by chronic RIC in this population, and we aimed to explore the influence of chronic RIC on collateral status evaluated by digital subtraction angiography in this population. The RICAS (Remote Ischemic Preconditioning on Collaterals of Atherosclerosis Stroke) study is a prospective, randomized, blind end point, multicenter study. Eligible patients with ischemic stroke of anterior circulation caused by large artery atherosclerosis, poor collateral compensation, and more than 1 month of symptom onset, are randomly assigned into experimental and control groups with a ratio of 1:1. The patients in the experiment group will receive treatment with RIC (bilateral upper limbs, for a total procedure time of 50 minutes, twice daily) for 1 year as an adjunct to guideline-based treatment, while patients in the control group only receive guideline-based treatment. A maximum of 300 patients (150 participants per group) are required to test the superiority hypothesis with 80% power (using a 2-sided α=0.05) to detect a 15% difference. Subgroup analyses for the primary end point will be performed on 8 prespecified subgroups by age, sex, ischemic event (acute ischemic stroke ore transient ischemic stroke), tandem lesion, history of hypertension, hypercholesterolemia, diabetes, and myocardial infarction. The primary outcome is the proportion of collateral status improvement, which is defined as an increase of ≥1 point on the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology score, as assessed by digital subtraction angiography at 12 months after randomization. The safety outcomes include RIC-related adverse events. This study may provide the direct evidence for the potential effect of chronic RIC treatment on the improvement of collateral status. URL: https://clinicaltrials.gov. Unique identifier: NCT06170944.

Abstract 48: Effect of Remote Ischemic Conditioning on Functional Outcomes in Patients With Supratentorial Intracerebral Hemorrhage: The Final Results of RICH-2 Randomized Controlled Clinical Trial

Abstract 48: Effect of Remote Ischemic Conditioning on Functional Outcomes in Patients With Supratentorial Intracerebral Hemorrhage: The Final Results of RICH-2 Randomized Controlled Clinical Trial

Abstract TP39: A Phase 2a randomized controlled trial of once-daily versus twice-daily remote ischemic conditioning in vascular cognitive impairment (TRIC-VCI)

Abstract TP39: A Phase 2a randomized controlled trial of once-daily versus twice-daily remote ischemic conditioning in vascular cognitive impairment (TRIC-VCI)

Abstract WMP2: A Trial of Patients Receiving Remote Ischemic Conditioning in Early Stroke (PRICES) in a Tertiary Hospital in the Philippines: An Open Label Study

Abstract WMP2: A Trial of Patients Receiving Remote Ischemic Conditioning in Early Stroke (PRICES) in a Tertiary Hospital in the Philippines: An Open Label Study

Abstract WMP9: The Effect Of Remote Ischemic Conditioning On Acute Infarct Growth In Patients With Acute Ischemic Stroke - Subgroup Analysis From The RESIST Trial

Abstract WMP9: The Effect Of Remote Ischemic Conditioning On Acute Infarct Growth In Patients With Acute Ischemic Stroke - Subgroup Analysis From The RESIST Trial

Abstract TMP109: Remote Ischemic Conditioning Treatment: A Study Report on Animal Stroke Model in Different Species, Sex, Age and Comorbidities from the Stroke Preclinical Assessment Network (SPAN)

Background: The Stroke Preclinical Assessment Network (SPAN), a multi-center network consisting of a coordinating center and testing laboratories, was created to enhance the rigor of preclinical research, including testing of potential therapies in animals of different species, sex, age, and co-morbidities, with blinding and randomization. SPAN evaluated six potential therapies with the goal of identifying one or more efficacious agents to advance toward a clinical trial. Remote ischemic post-conditioning (RIC) was selected as a candidate therapy for testing. Methods: In Stage I, young, healthy mixed-sex mice were randomized into treatment groups by the coordinating center. In Stage II, aged mice, mice with high-fat diet-induced obesity, and spontaneously hypertensive rats were utilized. Each stage included 25% of the study population and efficacy/futility was determined after each stage. RIC was bilaterally administered as the first session occurred immediately after reperfusion, and the second session occurred as close as possible to 12 ± 2 hours at post-MCAo, using an automated blood pressure cuff that delivered 200-mmHg to the hindlimbs for 4 cycles x 5 minutes/cycle and then once per day x 5 days under anesthesia. Sham-conditioned animals were treated with a cuff that did not inflate. The primary outcome measure was a modified corner test on days 7 and 30 post-stroke. MRI was performed at 48 hours and 30 days. Probabilistic index models, which adjusted for covariates of interest, were fit to estimate the probability of a lower corner test index (better outcome) between sham and RIC. Results: A total of 266 mice (132 sham, 134 RIC) were enrolled in the study, with 50 sham and 51 RIC-treated mice dying within 5 days of stroke. Analysis of all data revealed no significant differences in day 30 alternative corner test index between sham and RIC-treated mice after stroke in young, healthy mice (p=0.449), aged mice (p=0.079), mice with diet-induced obesity (p=0.135), or in spontaneously hypertensive rats (p=0.807). The secondary analysis found that RIC improved day 30 tissue infarction volume by MRI in young, healthy mice (p=0.024 vs. sham) but not in other co-morbid conditions. Conclusions: After advancing through Stages I and II, RIC was deemed futile at the end of Stage II, as determined by the modified corner test on day 30. The requirement for repeated daily general anesthesia during RIC administration may have been a complicated factor.