Remote ischemic conditioning combined with intravenous thrombolysis for acute ischemic stroke

He, Yaode; Guo, Zhen‐Ni; Chen, Qin; Jin, Hang; Zhang, Peng; Abuduxukuer, Reziya; Yang, Yi

doi:10.1002/acn3.51063

Cited by 32 publications

(39 citation statements)

References 22 publications

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“…None of the human trials succeeded in applying the intended RIC protocol; trials had low completion rates that were not taken into account in the data analysis and interpretation of results 32,33,37,38 . A recent study published following the completion of our final search reported to complete all intended cycles but reported no clinical effect of RIC 44 …”

Section: Discussionmentioning

confidence: 99%

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Translational challenges of remote ischemic conditioning in ischemic stroke – a systematic review

Hansen

Nielsen

Christoffersen

et al. 2021

Ann Clin Transl Neurol

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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.

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Section: Discussionmentioning

confidence: 99%

“… 32 , 33 , 37 , 38 A recent study published following the completion of our final search reported to complete all intended cycles but reported no clinical effect of RIC. 44 …”

Section: Discussionmentioning

confidence: 99%

Translational challenges of remote ischemic conditioning in ischemic stroke – a systematic review

Hansen

Nielsen

Christoffersen

et al. 2021

Ann Clin Transl Neurol

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show abstract

“…With respect to platelet function and the coagulation cascade, animal models have demonstrated the fibrinolytic and anticoagulant benefits of RIC [ 97 ]. However, this benefit has not been observed in humans [ 41 , 46 , 52 , 116 ]. Following the ERIC-PPCI/CONDI-2 trial, a subsequent sub-analysis of the study population was performed to look for fibrinolysis benefit, but no firm trends were observed, with the exception of a reduction in time to thrombosis at 48 h [ 41 ].…”

Section: Does Ric Mediate Innate Immune Cell Activity?mentioning

confidence: 99%

Does remote ischaemic conditioning reduce inflammation? A focus on innate immunity and cytokine response

Pearce¹,

Davidson²,

Yellon³

2021

Basic Res Cardiol

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The benefits of remote ischaemic conditioning (RIC) have been difficult to translate to humans, when considering traditional outcome measures, such as mortality and heart failure. This paper reviews the recent literature of the anti-inflammatory effects of RIC, with a particular focus on the innate immune response and cytokine inhibition. Given the current COVID-19 pandemic, the inflammatory hypothesis of cardiac protection is an attractive target on which to re-purpose such novel therapies. A PubMed/MEDLINE™ search was performed on July 13th 2020, for the key terms RIC, cytokines, the innate immune system and inflammation. Data suggest that RIC attenuates inflammation in animals by immune conditioning, cytokine inhibition, cell survival and the release of anti-inflammatory exosomes. It is proposed that RIC inhibits cytokine release via a reduction in nuclear factor kappa beta (NF-κB)-mediated NLRP3 inflammasome production. In vivo, RIC attenuates pro-inflammatory cytokine release in myocardial/cerebral infarction and LPS models of endotoxaemia. In the latter group, cytokine inhibition is associated with a profound survival benefit. Further clinical trials should establish whether the benefits of RIC in inflammation can be observed in humans. Moreover, we must consider whether uncomplicated MI and elective surgery are the most suitable clinical conditions in which to test this hypothesis.

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“…27 The primary aims for many of these studies are to establish whether RIPerC and/or early RIPostC is safe and can reduce stroke severity assessed by clinical and radiological indicators. Alongside this, several studies are investigating the feasibility of hyperacute RIC alongside intravenous thrombolysis (SERICT-AIS -NCT04027621 28 ; rTPA-RIC -NCT02886390; rTPA-RIC1 -NCT03231384; TRIPCAIS -NCT03218293) and ET (PROTECT-I -NCT03915782; REVISE-2 -NCT03045055; RICE-PAC -NCT03152799). While the most trials are investigating whether RIC in ischaemic stroke, a subset of studies are investigating RIC in intracerebral haemorrhage and subarachnoid haemorrhage (online supplemental material).…”

Section: Riperc and Early Ripostcmentioning

confidence: 99%

Remote ischaemic conditioning for stroke: unanswered questions and future directions

et al. 2021

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Remote ischaemic conditioning (RIC) refers to a process whereby periods of intermittent ischaemia, typically via the cyclical application of a blood pressure cuff to a limb at above systolic pressure, confers systemic protection against ischaemia in spatially distinct vascular territories. The mechanisms underlying this have not been characterised fully but have been shown to involve neural, hormonal and systemic inflammatory signalling cascades. Preclinical and early clinical studies have been promising and suggest beneficial effects of RIC in acute ischaemic stroke, symptomatic intracranial stenosis and vascular cognitive impairment. Through systematic searches of several clinical trials databases we identified 48 active clinical trials of RIC in ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage. We summarise the different RIC protocols and outcome measures studied in ongoing clinical trials and highlight which studies are most likely to elucidate the underlying biological mechanisms of RIC and characterise its efficacy in the near future. We discuss the uncertainties of RIC including the optimal frequency and duration of therapy, target patient groups, cost-effectiveness, the confounding impact of medications and the absence of a clinically meaningful biomarker of the conditioning response. With several large clinical trials of RIC expected to report their outcomes within the next 2 years, this review aims to highlight the most important studies and unanswered questions that will need to be addressed before this potentially widely accessible and low-cost intervention can be used in clinical practice.

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Remote ischemic conditioning combined with intravenous thrombolysis for acute ischemic stroke

Cited by 32 publications

References 22 publications

Translational challenges of remote ischemic conditioning in ischemic stroke – a systematic review

Translational challenges of remote ischemic conditioning in ischemic stroke – a systematic review

Does remote ischaemic conditioning reduce inflammation? A focus on innate immunity and cytokine response

Remote ischaemic conditioning for stroke: unanswered questions and future directions

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