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

Appleton, Jason P; O'Sullivan, Saoirse E; Hedstrom, Amanda; May, Jane A; Donnelly, Richard; Sprigg, Nikola; Bath, Philip M.; England, Timothy J.

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 24h 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.

Citation

Appleton, J. P., O'Sullivan, S. E., Hedstrom, A., May, J. A., Donnelly, R., Sprigg, N., …England, T. J. (2021). Blood markers in remote ischaemic conditioning for acute ischaemic stroke: data from the REmote ischaemic Conditioning After Stroke Trial. European Journal of Neurology, 28(4), 1225-1233. https://doi.org/10.1111/ene.14650

• Journal Article Type: Article
• Acceptance Date: Nov 15, 2020
• Online Publication Date: Dec 14, 2020
• Publication Date: 2021-04
• Deposit Date: Nov 20, 2020
• Publicly Available Date: Dec 15, 2021
• Journal: European Journal of Neurology
• Print ISSN: 1351-5101
• Electronic ISSN: 1468-1331
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 28
• Issue: 4
• Pages: 1225-1233
• DOI: https://doi.org/10.1111/ene.14650
• Keywords: Remote ischaemic conditioning ,Ischaemic stroke, Biomarkers, Serum amyloid protein, Nitric oxide
• Public URL: https://nottingham-repository.worktribe.com/output/5055435
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/ene.14650