Abstract
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). 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). 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. 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.
Highlights
Blood samplesRemote ischaemic per-conditioning (RIC)—inducing ischaemia/ reperfusion distant to the brain—in experimental ischaemic stroke is neuroprotective [1,2,3]
Higher S100-β levels at pre-intervention, post-intervention and day 4 were significantly moderately correlated with worse National Institutes of Health Stroke Scale (NIHSS) scores at day 90, but not modified Rankin Scale (mRS) or Barthel index (BI) (Table 2, Figure S1)
In the first analysis assessing blood biomarkers in RIC in acute ischaemic stroke patients, it has been demonstrated that RIC reduced serum amyloid protein (SAP) and tissue necrosis factor α (TNF-α) levels
Summary
Remote ischaemic per-conditioning (RIC)—inducing ischaemia/ reperfusion distant to the brain—in experimental ischaemic stroke is neuroprotective [1,2,3]. There is a paucity of data on the effects of RIC on potential mechanistic pathways in human patients with acute ischaemic stroke. Neuroprotective or vascular markers are influenced by RIC in acute ischaemic stroke is unknown. Several inflammation-related biomarkers including adipsin [5] α2-macroglobulin (A2 M), serum amyloid protein (SAP) [6] and E-selectin [7] have been associated with clinical outcome in stroke patients. Whether these or other elements of inflammatory pathways are influenced by RIC is unclear. Given the limited data regarding RIC and biomarkers in ischaemic stroke patients, in exploratory and hypothesis-generating analyses the effect of RIC on plasma biomarkers and the correlation of these biomarkers with clinical outcomes in acute ischaemic stroke patients in RECAST-1 were assessed
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