Remote Ischemic Conditioning: Feasible and Potentially Beneficial for Ischemic Stroke.
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ABSTRACT:
SUBMITTER: Hess DC
PROVIDER: S-EPMC9832743 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
Publications
Remote Ischemic Conditioning: Feasible and Potentially Beneficial for Ischemic Stroke.
Hess David C DC Blauenfeldt Rolf A RA Andersen Grethe G
JAMA 20220801 7
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Project description:Remote ischemic conditioning (RIC) is a noninvasive procedure whereby several periods of ischemia are induced in a limb. Although there is growing interest in using RIC to improve stroke recovery, preclinical RIC research has focused exclusively on neuroprotection, using male animals and the intraluminal suture stroke model, and delivered RIC at times not relevant to either brain repair or behavioral recovery. In alignment with the Stroke Recovery and Rehabilitation Roundtable, we address these shortcomings. First, a standardized session (5-minute inflation/deflation, 4 repetitions) of RIC was delivered using a cuff on the contralesional hindlimb in both male and female Sprague-Dawley rats. Using the endothelin-1 stroke model, RIC was delivered once either prestroke (18 hours before, pre-RIC) or poststroke (4 hours after, post-RIC), and infarct volume was assessed at 24 hours poststroke using magnetic resonance imaging. RIC was delivered at these times to mimic the day before a surgery where clots are possible or as a treatment similar to tissue plasminogen activator, respectively. Pre-RIC reduced infarct volume by 41% compared with 29% with post-RIC. RIC was neuroprotective in both sexes, but males had a 46% reduction of infarct volume compared with 23% in females. After confirming the acute efficacy of RIC, we applied it chronically for 4 weeks, beginning 5 days poststroke. This delayed RIC failed to enhance poststroke behavioral recovery. Based on these findings, the most promising application of RIC is during the hyperacute and early acute phases of stroke, a time when other interventions such as exercise may be contraindicated.
| S-EPMC8135236 | biostudies-literature
Project description:In remote ischemic conditioning (RIC), brief, reversible episodes of ischemia with reperfusion in one vascular bed, tissue, or organ confer a global protective phenotype and render remote tissues and organs resistant to ischemia/reperfusion injury. The peripheral stimulus can be chemical, mechanical, or electrical and involves activation of peripheral sensory nerves. The signal transfer to the heart or other organs is through neuronal and humoral communications. Protection can be transferred, even across species, with plasma-derived dialysate and involves nitric oxide, stromal derived factor-1?, microribonucleic acid-144, but also other, not yet identified factors. Intracardiac signal transduction involves: adenosine, bradykinin, cytokines, and chemokines, which activate specific receptors; intracellular kinases; and mitochondrial function. RIC by repeated brief inflation/deflation of a blood pressure cuff protects against endothelial dysfunction and myocardial injury in percutaneous coronary interventions, coronary artery bypass grafting, and reperfused acute myocardial infarction. RIC is safe and effective, noninvasive, easily feasible, and inexpensive.
| S-EPMC4297315 | biostudies-other
Project description:BackgroundRemote ischemic conditioning (RIC) has shown an impressive neuroprotective effect on acute ischemic stroke (AIS) in animal experiments. But whether chronic RIC improves long-term functional outcomes remains unclear.Materials and methodsWe performed a non-randomized controlled trial. Eligible patients (aged 18 -80 y) with hemiplegia caused by AIS were allocated to the RIC group and the control group. All participants received normal protocol rehabilitation therapy. Patients in the RIC group underwent RIC twice daily for 90 days. The outcome included the 90-day Fugl-Meyer Assessment (FMA) scores and modified Rankin's scale (mRS) scores, as well as changes in angiogenesis-related factors in serum from baseline to 90 days.ResultsTwenty-seven patients were included in the analysis (13 in the RIC group and 14 in the control group). There was no significant difference in 90-day total FMA scores between the two groups. Lower limb FMA scores at day 90 were significantly higher in the RIC group (32.8±8.7 vs. 24.8±5.4, adjusted P =0.042). The proportion of favorable outcome (mRS<2) was higher in the RIC group than that in the control group, but no significant difference was detected (8 [61.5%] vs. 7 [50%], P =0.705). A significant increase has been found in the level of epidermal growth factor (EGF) in serum (9.4 [1.1 to 25.7] vs. -8.7 [-15.1 to 4.7], P =0.036) after chronic RIC procedure.ConclusionThis study investigated the role that RIC plays in AIS recovery, especially in motor function. RIC may have beneficial effects on lower limbs recovery by enhancing the EGF level. The effect of RIC on motor recovery should be further validated in future studies.
| S-EPMC10627541 | biostudies-literature
Project description:ObjectiveThe objective of this study was to investigate the safety and efficacy of remote ischemic conditioning (RIC) combined with intravenous thrombolysis (IVT) in the treatment of acute ischemic stroke (AIS).MethodsPatients with AIS who underwent IVT were enrolled and 1:1 randomized to the RIC group and sham-RIC group in this study. RIC (or sham-RIC) was performed twice within 6-24 h of IVT. The subjects in the two groups were followed up for 90 days. The safety outcome included the ratio of hemorrhagic transformation (HT), adverse events during the follow-up, blood pressure within the first 24 h after IVT, and laboratory tests 24 h after IVT. The efficacy outcome included the modified Rankin Scale (mRS) score, National Institute of Health Stroke Scale (NIHSS) score during the follow-up, and level of high-sensitivity C-reactive protein (hs-CRP) tested 24 h after IVT.ResultsForty-nine patients (24 in the RIC group and 25 in the sham-RIC group) were recruited. No significant difference was observed in the ratio of HT, adverse events, blood pressure, coagulation function or liver function between groups. In addition, there was no significant difference in mRS score and NIHSS score during the follow-up between groups. However, patients in the RIC group exhibited a significant lower level of hs-CRP compared with the control group (P = 0.048).InterpretationRIC combined with IVT is safe in the treatment of AIS. The neuroprotective and anti-inflammatory effects of this therapy warrant further study on a larger scale.
| S-EPMC7318096 | biostudies-literature
Project description:ObjectiveWe aimed to evaluate the safety and effectiveness of short-term remote ischemic postconditioning (RIPC) in acute stroke monkey models.MethodsAcute stroke monkeys were allocated to four groups based on the number of limbs exposed to RIPC. RIPC was initiated by 5-min cuff inflation/deflation cycles of the target limb(s) for 5-10 bouts. Vital signs, skin integrity, brain MRI, and serum levels of cardiac enzymes (myoglobin, creatine kinase [CK], CK-muscle/brain [CK-MB]), one inflammatory marker (high-sensitivity C-reactive protein [hsCRP], and one endothelial injury marker (von Willebrand factor [vWF]) were assessed. Spetzler scores were used to assess neurological function.ResultsNo significant differences in vital signs or local skin integrity were found. Short-term RIPC did not reduce infarct volume under any condition at the 24th hour after stroke. However, neurological function improved in multi-limb RIPC compared with sham and single-limb RIPC at the 30th day follow-up after stroke. Myoglobin, CK, and CK-MB levels were reduced after multi-limb RIPC, regardless of the number of bouts. Moreover, multi-limb RIPC produced a greater diminution in CK-MB levels, whereas two-limb RIPC was more effective in reducing serum CK levels at the 24th hour after stroke. hsCRP increased after 5 bouts of multi-limb RIPC before decreasing below baseline and single-limb RIPC levels. Serum vWF was decreased at later time points after RIPC in all RIPC groups.ConclusionsStroke monkeys in hyperacute stage may benefit from short-term RIPC; however, whether this intervention can be translated into clinical use in patients with acute ischemic stroke warrants further study.
| S-EPMC6389742 | biostudies-literature
Project description:AimsA post hoc analysis of RICAMIS trial to evaluate functional outcomes in relation to patient age.MethodsPatients in RICAMIS were divided into six age groups. The primary outcome was excellent functional outcome at 90 days, defined as modified Rankin Scale (mRS) score of 0-1. Compared with patients receiving usual care alone, we investigated the association of remote ischemic conditioning (RIC) effect with functional outcomes in each group and the interaction between RIC effect and age.ResultsOf 1776 patients, 498 were assigned to <60 years, 326 to 60 to <65 years, 325 to 65 to <70 years, 278 to 70 to <75 years, 206 to 75 to <80 years, and 143 to ≥80 years. Higher proportions of primary outcome were found associated with RIC in <60 years group (72.6% vs. 64.8%; adjusted risk difference [RD], 6.8%; 95% CI, -1.6% to 15.1%; p = 0.11), 60 to <65 years group (70.7% vs. 67.1%; adjusted RD, 3.1%; 95% CI, -7.2% to 13.3%; p = 0.56), 65 to <70 years group (70.5% vs. 63.6%; adjusted RD, 3.5%; 95% CI, -6.8% to 13.8%; p = 0.51), 70 to <75 years group (59.7% vs. 54.9%; adjusted RD, 4.7%; 95% CI, -7.1% to 16.4%; p = 0.61), 75 to <80 years group (61.5% vs. 55.9%; adjusted RD, 5.7%; 95% CI, -7.8% to 19.1%; p = 0.41), and ≥ 80 years group (59.2% vs. 59.7%; adjusted RD, -2.6%; 95% CI, -18.8% to 13.5%; p = 0.75). No significant interaction between RIC effect and age was found among groups.ConclusionsThis is the first report that RIC effect may be attenuated with increasing age in patients with acute moderate ischemic stroke with respect to functional outcome.
| S-EPMC10916442 | biostudies-literature
Project description: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.
| S-EPMC10903142 | biostudies-literature
Project description:Remote ischemic conditioning (RIC) has well-established cardioprotective effects in preclinical studies and promising results in preclinical stroke research. Effective translation from preclinical studies to clinical trials has yet to be accomplished, perhaps because of the use of multiple applications of RIC (e.g., pre-, per-, or post-conditioning) in preclinical studies by both invasive and non-invasive protocols, some of which not clinically applicable. Our systematic review conformed to PRISMA guidelines and addressed differences in clinically relevant RIC applications and outcomes between preclinical and clinical studies. We retrieved a total of 30 studies (8 human; 22 animal) that met the inclusion criteria of testing clinically relevant procedures; namely, non-invasive and per- or post-conditioning protocols. Per-conditioning was applied in 6 animal and 3 human studies, post-conditioning was applied in 16 animal and 5 human studies, and both conditioning methods were applied in 2 animal studies. Application of RIC varied between human and animal studies regarding initiation, duration, repetition, and number of limbs included. Study designs did not systematically apply blinding, randomization, or placebo controls. On only a few occasions did preclinical studies include animals with clinically relevant comorbidities. Clinical trials were challenged by not completing the intended number of RIC cycles or addressing this deficit in the data analysis. Consistency and transferability of methods used for positive animal studies and subsequent human studies are essential for the optimal translation of results. Consensus on preclinical and clinical RIC procedures should be reached for a full understanding of the possible beneficial effects of RIC treatment in stroke.
| S-EPMC8351389 | biostudies-literature
Project description:Acute myocardial infarction and ischemic stroke are leading causes of morbidity and mortality worldwide. Although reperfusion therapies have greatly improved the outcomes of patients with these conditions, many patients die or are severely disabled despite complete reperfusion. It is therefore important to identify interventions that can prevent progression to ischemic necrosis and limit ischemia-reperfusion injury. A possible strategy is ischemic conditioning, which consists of inducing ischemia - either in the ischemic organ or in another body site [i.e., remote ischemic conditioning (RIC), e.g., by inflating a cuff around the patient's arm or leg]. The effects of ischemic conditioning have been studied, alone or in combination with revascularization techniques. Based on the timing (before, during, or after ischemia), RIC is classified as pre-, per-/peri-, or post-conditioning, respectively. In this review, we first highlight some pathophysiological and clinical similarities and differences between cardiac and cerebral ischemia. We report evidence that RIC reduces circulating biomarkers of myocardial necrosis, infarct size, and edema, although this effect appears not to translate into a better prognosis. We then review cutting-edge applications of RIC for the treatment of ischemic stroke. We also highlight that, although RIC is a safe procedure that can easily be implemented in hospital and pre-hospital settings, its efficacy in patients with ischemic stroke remains to be proven. We then discuss possible methodological issues of previous studies. We finish by highlighting some perspectives for future research, aimed at increasing the efficacy of ischemic conditioning for improving tissue protection and clinical outcomes, and stratifying myocardial infarction and brain ischemia patients to enhance treatment feasibility.
| S-EPMC8576053 | biostudies-literature
Project description:ObjectiveRemote ischemic conditioning (RIC) has been demonstrated to be safe and feasible for patients with acute ischemic stroke (AIS), as well as for those receiving intravenous thrombolysis. We assessed the safety and feasibility of RIC for AIS patients undergoing endovascular treatment (ET).MethodsWe conducted a pilot study with patients with AIS who were suspected of having an emergent large-vessel occlusion in the anterior circulation and who were scheduled for ET within 6 hours of ictus. Four cycles of RIC were performed before recanalization, immediately following recanalization, and once daily for the subsequent 7 days. The primary outcome was any serious RIC-related adverse events.ResultsTwenty subjects, aged 66.1 ± 12.1 years, were recruited. No subject experienced serious RIC-related adverse events. The intracranial pressure, cranial perfusion pressure, mean arterial pressure, heart rate, middle cerebral artery peak systolic flow velocity, and pulsatility index did not change significantly before, during, or after the limb ischemia (P > 0.1 for all). Of 80 cycles, 71 (89%) were completed before recanalization and 80 (100%) were completed immediately after recanalization; 444 of 560 cycles (78%) were completed within 7 days posttreatment. No patients had to stop RIC because it affected routine clinical managements. Six subjects (30%) experienced intracerebral hemorrhage, which was symptomatic in one case (5%). At the 3-month follow-up, 11 subjects (55%) had achieved functional independence, and two subjects (10%) died.InterpretationRIC appears to be safe and feasible for patients with AIS undergoing ET. Investigations are urgently needed to determine the efficacy of RIC in this patient population.
| S-EPMC6043766 | biostudies-literature