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Randomized Controlled Trial
. 2025 Mar;56(3):603-612.
doi: 10.1161/STROKEAHA.124.048976. Epub 2025 Jan 30.

Effect of Remote Ischemic Conditioning on the Form and Function of Red Blood Cells in Patients With Acute Ischemic Stroke

Rolf Ankerlund Blauenfeldt  1   2 , Jennifer Waller  3 , Kim Ryun Drasbek  4 , Jesper Nørgaard Bech  2   5 , Anne-Mette Hvas  6 , Julie Brogaard Larsen  6 , Morten Nørgaard Andersen  7   2 , Marlene Christina Nielsen  6 , Maria Kjølhede  1 , Mathilde Kjeldsen  5 , Martin Faurholdt Gude  2   8 , Mohammad Badruzzaman Khan  9 , Babak Baban  9 , Grethe Andersen  1   2 , David Charles Hess  9
Affiliations
Randomized Controlled Trial

Effect of Remote Ischemic Conditioning on the Form and Function of Red Blood Cells in Patients With Acute Ischemic Stroke

Rolf Ankerlund Blauenfeldt et al. Stroke. 2025 Mar.

Abstract

Background: Remote ischemic conditioning (RIC) is a simple and low-cost intervention that is thought to increase collateral blood flow through the vasodilatory effects of nitric oxide (NO) produced by the endothelium and red blood cells (RBCs). This study aims to investigate whether RIC affects RBC deformability and levels of NO and nitrite in patients with ischemic stroke.

Methods: This is a predefined substudy to the RESIST (Remote Ischemic Conditioning in Patients With Acute Stroke Trial) randomized clinical trial conducted in Denmark. RIC was started in the ambulance and continued at the hospital for seven days. Blood samples were collected at different time points: prehospital in the ambulance, in-hospital upon arrival, 2 hours postadmission, and 24 hours postadmission. RBC deformability and erythrocyte aggregation rate were assessed using ektacytometry, NO using flowcytometry, and nitrite content using ozone chemiluminescence.

Results: Of 1500 prehospital randomized patients, 486 patients were included in this study between July 28, 2020, and November 11, 2023, and had blood samples taken. Of these, 249 (51%) had AIS, and here RIC treatment was not associated with increased RBC maximal deformability (RIC, 0.549; sham, 0.548; P=0.31), RBC NO (RIC, 35 301 median fluorescence intensity; sham, 34979 median fluorescence intensity; P=0.89), or nitrite (RIC, 0.036 µmol/L; sham, 0.034 µmol/L; P=0.38), but RIC treatment was associated with a significantly reduced aggregation pressure and a slower erythrocyte aggregation rate (RIC, 323.76 millipascal; sham, 352.74 millipascal; P=0.0113).

Conclusions: Prehospital and in-hospital RIC significantly reduced erythrocyte aggregation rate in patients with acute ischemic stroke, while there was no change in RBC deformability, NO content, or whole blood nitrite levels.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03481777.

Keywords: erythrocytes; ischemic stroke; nitric oxide; nitrites.

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Conflict of interest statement

Dr Blauenfeldt reports lecture fees from Bayer, Pfizer, and Novo Nordisk outside the submitted work. Dr Hess reports receiving grants from the National Institutes of Health biomarker substudy of the parent clinical trial during the conduct of the study; personal fees from Athersys Inc’s scientific advisory board outside the submitted work; and holding a patent for multipotent stem cells in neurological disease issued to the Medical College of Georgia, Augusta University by Athersys Inc. Dr Larsen reports lecture fees from Bristol-Myers Squibb (paid to her institution), lecture fees from Merck (paid to her institution), and travel support from Bayer outside the submitted work. Dr Bech is on an advisory board for Bayer, unrelated to the submitted work. The other authors report no conflicts.

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