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远程缺血后适应治疗急性缺血性脑卒中的血液标志物:来自脑卒中后远程缺血后适应试验的数据。

Blood markers in remote ischaemic conditioning for acute ischaemic stroke: data from the REmote ischaemic Conditioning After Stroke Trial.

机构信息

Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK.

Stroke, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

出版信息

Eur J Neurol. 2021 Apr;28(4):1225-1233. doi: 10.1111/ene.14650. Epub 2020 Dec 14.

Abstract

BACKGROUND AND PURPOSE

Remote ischaemic per-conditioning (RIC) is neuroprotective in experimental ischaemic stroke. Several neurohumoral, vascular and inflammatory mediators are implicated. The effect of RIC on plasma biomarkers was assessed using clinical data from the REmote ischaemic Conditioning After Stroke Trial (RECAST-1).

METHODS

RECAST-1 was a pilot sham-controlled blinded trial in 26 patients with ischaemic stroke, randomized to receive four 5-min cycles of RIC within 24 h of ictus. Plasma taken pre-intervention, immediately post-intervention and on day 4 was analysed for nitric oxide (nitrate/nitrite) using chemiluminescence and all other biomarkers by multiplex analysis. Biomarkers were correlated with clinical outcome (day 90 National Institutes of Health Stroke Scale, modified Rankin Scale, Barthel index).

RESULTS

Remote ischaemic per-conditioning reduced serum amyloid protein (SAP) and tissue necrosis factor α (TNF-α) levels from pre- to post-intervention (n = 13, two-way ANOVA, p < 0.05). Overall (n = 26), increases in SAP pre- to post-intervention and pre-intervention to day 4 were moderately correlated with worse day 90 clinical outcomes. No consistent significant changes over time, or by treatment, or correlations with outcome were seen for other biomarkers.

CONCLUSIONS

Remote ischaemic per-conditioning reduced SAP and TNF-α levels from pre- to post-intervention. Increases in plasma levels of SAP were associated with worse clinical outcomes after ischaemic stroke. Larger studies assessing biomarkers and the safety and efficacy of RIC in acute ischaemic stroke are warranted to further understand these relationships.

摘要

背景与目的

远程缺血预处理(RIC)对实验性缺血性卒中具有神经保护作用。几种神经体液、血管和炎症介质都与 RIC 有关。使用 REMOTE ISCHAEMIC CONDITIONING AFTER STROKE TRIAL(RECAST-1)的临床数据评估 RIC 对血浆生物标志物的影响。

方法

RECAST-1 是一项在 26 例缺血性卒中患者中进行的初步假对照盲法试验,患者随机分为在卒中后 24 小时内接受 4 个 5 分钟周期的 RIC。在干预前、干预后立即和第 4 天采集血浆,使用化学发光法分析一氧化氮(硝酸盐/亚硝酸盐),并通过多重分析分析所有其他生物标志物。生物标志物与临床结局(第 90 天国立卫生研究院卒中量表、改良 Rankin 量表、Barthel 指数)相关。

结果

RIC 降低了血清淀粉样蛋白(SAP)和组织坏死因子-α(TNF-α)水平(n=13,双因素方差分析,p<0.05)。总体而言(n=26),SAP 在干预前到干预后的增加以及干预前到第 4 天的增加与第 90 天的临床结局较差中度相关。没有看到其他生物标志物在时间、治疗或与结局的相关性方面有一致的显著变化。

结论

RIC 降低了干预前到干预后的 SAP 和 TNF-α 水平。SAP 血浆水平的升高与缺血性卒中后的临床结局较差相关。需要更大的研究来评估生物标志物以及 RIC 在急性缺血性卒中中的安全性和疗效,以进一步了解这些关系。

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