Timothy J England1, Amanda Hedstrom2, Saoirse O'Sullivan2, Richard Donnelly2, David A Barrett2, Sarir Sarmad2, Nikola Sprigg2, Philip M Bath2. 1. From the Department of Vascular Medicine, Division of Medical Sciences and GEM, School of Medicine (T.J.E., A.H., S.O., R.D.), Centre for Analytical Bioscience, School of Pharmacy (D.A.B., S.S.), and Stroke Trials Unit, Division of Clinical Neuroscience, School of Medicine (N.S., P.M.B.), University of Nottingham, United Kingdom. timothy.england@nottingham.ac.uk. 2. From the Department of Vascular Medicine, Division of Medical Sciences and GEM, School of Medicine (T.J.E., A.H., S.O., R.D.), Centre for Analytical Bioscience, School of Pharmacy (D.A.B., S.S.), and Stroke Trials Unit, Division of Clinical Neuroscience, School of Medicine (N.S., P.M.B.), University of Nottingham, United Kingdom.
Abstract
BACKGROUND AND PURPOSE: Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke. METHODS: We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures. RESULTS:Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75-9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group: 2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group (P=0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5-5) versus 3 (interquartile range, 2-9.5; P=0.04); RIC augmented plasma HSP27 (heat shock protein 27; P<0.05, repeated 2-way ANOVA) and phosphorylated HSP27 (P<0.001) but not plasma S100-β, matrix metalloproteinase-9, endocannabinoids, or arterial compliance. CONCLUSIONS:RIC after acute stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com. Unique identifier: ISRCTN86672015.
RCT Entities:
BACKGROUND AND PURPOSE: Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke. METHODS: We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures. RESULTS: Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75-9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group: 2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group (P=0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5-5) versus 3 (interquartile range, 2-9.5; P=0.04); RIC augmented plasma HSP27 (heat shock protein 27; P<0.05, repeated 2-way ANOVA) and phosphorylated HSP27 (P<0.001) but not plasma S100-β, matrix metalloproteinase-9, endocannabinoids, or arterial compliance. CONCLUSIONS:RIC after acute stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com. Unique identifier: ISRCTN86672015.
Authors: Seyed Mohammad Seyedsaadat; Leonardo Rangel Castilla; Giuseppe Lanzino; Harry J Cloft; Daniel J Blezek; Amy Theiler; Ramanathan Kadirvel; Waleed Brinjikji; David F Kallmes Journal: Neuroradiol J Date: 2019-04-03
Authors: Muhammad Nadeem; Adam Kindelin; Laura Mahady; Kanchan Bhatia; Md Nasrul Hoda; Andrew F Ducruet; Saif Ahmad Journal: Neuromolecular Med Date: 2020-11-13 Impact factor: 3.843
Authors: Allison S Hyngstrom; Jennifer N Nguyen; Michael T Wright; Sergey S Tarima; Brian D Schmit; David D Gutterman; Matthew J Durand Journal: J Appl Physiol (1985) Date: 2020-10-22