Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke

An, Jiaqi; Cheng, Yawen; Guo, Yichen; Wang, Meng; Gong, Minjie; Tang, Yujie; Yuan, Xingyun; Song, Wenfeng; Mu, Chunying; Zhang, Aifeng; Saguner, Ardan M.; Li, Guoliang; Luo, Gaoxing

doi:10.1212/wnl.0000000000010884

Cited by 50 publications

(50 citation statements)

References 32 publications

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“…The interest of RIC in AIS has emerged in the last years. Three clinical trials have evaluated different strategies of RIC among AIS with mixed results 13 – 15 . In parallel, several clinical trials are now ongoing to investigate the efficacy of RIC in patients with acute stroke 16 .…”

Section: Introductionmentioning

confidence: 99%

Preclinical evidence of remote ischemic conditioning in ischemic stroke, a metanalysis update

Torres

Quintana-Luque

Arqué

et al. 2021

Sci Rep

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Remote ischemic conditioning (RIC) is a promising therapeutic approach for ischemic stroke patients. It has been proven that RIC reduces infarct size and improves functional outcomes. RIC can be applied either before ischemia (pre-conditioning; RIPreC), during ischemia (per-conditioning; RIPerC) or after ischemia (post-conditioning; RIPostC). Our aim was to systematically determine the efficacy of RIC in reducing infarct volumes and define the cellular pathways involved in preclinical animal models of ischemic stroke. A systematic search in three databases yielded 50 peer-review articles. Data were analyzed using random effects models and results expressed as percentage of reduction in infarct size (95% CI). A meta-regression was also performed to evaluate the effects of covariates on the pooled effect-size. 95.3% of analyzed experiments were carried out in rodents. Thirty-nine out of the 64 experiments studied RIPostC (61%), sixteen examined RIPreC (25%) and nine tested RIPerC (14%). In all studies, RIC was shown to reduce infarct volume (− 38.36%; CI − 42.09 to − 34.62%) when compared to controls. There was a significant interaction caused by species. Short cycles in mice significantly reduces infarct volume while in rats the opposite occurs. RIPreC was shown to be the most effective strategy in mice. The present meta-analysis suggests that RIC is more efficient in transient ischemia, using a smaller number of RIC cycles, applying larger length of limb occlusion, and employing barbiturates anesthetics. There is a preclinical evidence for RIC, it is safe and effective. However, the exact cellular pathways and underlying mechanisms are still not fully determined, and its definition will be crucial for the understanding of RIC mechanism of action.

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Section: Introductionmentioning

confidence: 99%

Preclinical evidence of remote ischemic conditioning in ischemic stroke, a metanalysis update

Torres

Quintana-Luque

Arqué

et al. 2021

Sci Rep

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“…Four trials investigated the use of rPerc in stroke patients receiving reperfusion therapy: two combining rPerc with IVT, and two trials also treating patients with EVT (see paragraph on neuroprotection and EVT). In 2020 a single center trial ( n = 68) reported significant results in a trial of rPerc in which patients with AIS were treated with IVT and subsequent ischemic perconditioning ( 37 ). Excellent recovery (mRS 0–1) at 3 months was obtained in 72% of patients in the rPerc group vs. 50% in controls (adjusted risk ratio, 9.85; 95%CI, 1.5 to 63.2), though patients with severe stroke (NIHSS >24) were excluded from this trial.…”

Section: Studies Combining Neuroprotection and Ivtmentioning

confidence: 99%

Systematic Review - Combining Neuroprotection With Reperfusion in Acute Ischemic Stroke

Vos¹,

Geraedts

Lugt

et al. 2022

Front. Neurol.

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BackgroundClinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective treatments. This systematic review provides an overview of efficacy of neuroprotective agents in combination with reperfusion therapy in AIS.MethodsA literature search was performed on the following databases, namely PubMed, Embase, Web of Science, Cochrane Library, Emcare. All databases were searched up to September 23rd 2021. All randomized controlled trials in which patients were treated with neuroprotective strategies within 12 h of stroke onset in combination with intravenous thrombolysis (IVT), endovascular therapy (EVT), or both were included.ResultsWe screened 1,764 titles/abstracts and included 30 full reports of unique studies with a total of 16,160 patients. In 15 studies neuroprotectants were tested for clinical efficacy, where all patients had to receive reperfusion therapies, either IVT and/or EVT. Heterogeneity in reported outcome measures was observed. Treatment was associated with improved clinical outcome for: 1) uric acid in patients treated with EVT and IVT, 2) nerinetide in patients who underwent EVT without IVT, 3) imatinib in stroke patients treated with IVT with or without EVT, 4) remote ischemic perconditioning and IVT, and 5) high-flow normobaric oxygen treatment after EVT, with or without IVT.ConclusionStudies specifically testing effects of neuroprotective agents in addition to IVT and/or EVT are scarce. Future neuroprotection studies should report standardized functional outcome measures and combine neuroprotective agents with reperfusion therapies in AIS or aim to include prespecified subgroup analyses for treatment with IVT and/or EVT.

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“…Концепция дистанционного посткондиционирования предполагает более слабое, но более простое в осуществлении воздействие. Локальная ишемия в другом органе (обычноконечности) приводит к образованию цитокинов и паракринных агентов, которые с кровотоком могут попасть в другие органы и увеличить их устойчивость к повреждающим воздействиям [143][144][145]. Обычно такие эффекты имеют небольшую амплитуду, и в настоящее время этот подход также не нашел широкого применения в клинической практике.…”

Section: свободные радикалы при ишемическом повреждении мозгаunclassified

Brain acute ischemia mechanisms: implications to experimental and clinical treatment

Ivanov

Гаврилова

Koshelev

2021

Regional blood circulation and microcirculation

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We have reviewed current understanding of ischemic brain damage and the main therapeutic approaches. Pathological factors affecting the survival of neurons and glial cells in the focus of ischemia are outlined: depolarization, cytotoxic and vasogenic edema, calcium overload, excitotoxicity, inflammation, free radical damage. Effective and rapid reperfusion significantly improves patient’s survival and functional outcomes, but other approaches to brain infarction treatment did not approve their effectiveness in large clinical trials. Dozens of drugs (neuroprotectors) are being studied in order to compensate isolated pathological brain ischemia pathways and to increase cellular survival, but they were ineffective in large clinical trials.The reason for the ineffectiveness of neuroprotective drugs may be a lack of understanding of the drug targets real importance. Many drugs that have shown promising results in preclinical studies have not been studied in large clinical trials until now. Additional pathogenetic mechanisms revealed in the last decade expand our knowledge about the brain infarction and may become promising directions for the development of new therapeutic approaches.

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Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke

Cited by 50 publications

References 32 publications

Preclinical evidence of remote ischemic conditioning in ischemic stroke, a metanalysis update

Preclinical evidence of remote ischemic conditioning in ischemic stroke, a metanalysis update

Systematic Review - Combining Neuroprotection With Reperfusion in Acute Ischemic Stroke

Brain acute ischemia mechanisms: implications to experimental and clinical treatment

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