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

Babak Baban, Jennifer Waller, Grethe Andersen, Anne-Mette Hvas, Jesper Nørgaard Bech, Rolf Ankerlund Blauenfeldt, Kim Ryun Drasbek, Julie Brogaard Larsen, Morten Nørgaard Andersen, Marlene Christina Nielsen, Maria Kjølhede, Mathilde Kjeldsen, Martin Faurholdt Gude, Mohammad Badruzzaman Khan, David Charles Hess

Journal: Stroke 2025;56(3):603-612

PMID: 39882626

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; =0.31), RBC NO (RIC, 35 301 median fluorescence intensity; sham, 34979 median fluorescence intensity; =0.89), or nitrite (RIC, 0.036 µmol/L; sham, 0.034 µmol/L; =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; =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.

Address: Department of Neurology (R.A.B., M. Kjølhede, G.A.), Aarhus University Hospital, Denmark.; Department of Clinical Medicine (R.A.B., J.N.B., M.N.A., M.F.G., G.A.), Aarhus University, Denmark.; Department of Family and Community Medicine (J.W.), Medical College of Georgia, Augusta University.; Center for Functionally Integrative Neuroscience (K.R.D.), Aarhus University, Denmark.; Department of Clinical Medicine (R.A.B., J.N.B., M.N.A., M.F.G., G.A.), Aarhus University, Denmark.; University Clinic in Nephrology and Hypertension, Gødstrup Regional Hospital, Herning, Denmark (J.N.B., M. Kjeldsen).; Center for Thrombosis and Hemostasis, Department of Clinical Biochemistry (A.-M.H., J.B.L., M.C.N.), Aarhus University Hospital, Denmark.; Department of Hematology (M.N.A.), Aarhus University Hospital, Denmark.; Department of Clinical Medicine (R.A.B., J.N.B., M.N.A., M.F.G., G.A.), Aarhus University, Denmark.; Department of Neurology (R.A.B., M. Kjølhede, G.A.), Aarhus University Hospital, Denmark.; University Clinic in Nephrology and Hypertension, Gødstrup Regional Hospital, Herning, Denmark (J.N.B., M. Kjeldsen).; Department of Clinical Medicine (R.A.B., J.N.B., M.N.A., M.F.G., G.A.), Aarhus University, Denmark.; Pre-hospital Emergency Medical Services, Central Denmark Region, Aarhus, Denmark (M.F.G.).; Department of Neurology (M.B.K., B.B., D.C.H.), Medical College of Georgia, Augusta University.
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