Abstract Body: 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 (RBC). This study aims to investigate whether RIC affects RBC deformability and levels of NO and nitrite in ischemic stroke patients.

Methods:
This is a predefined sub-study to the RESIST randomized clinical trial. RIC was started in the ambulance and continued at the hospital for seven days. Patients with a prehospital putative stroke and symptom duration <4 hours could be included in this biomarker study. Blood-samples were collected at different time points: Prehospital in the ambulance, in-hospital upon arrival, 2 hours post-admission, 24 hours post-admission. RBC deformability and erythrocyte aggregation rate were assessed using ektacytometry, NO using flowcytometry, and nitrite content using ozone chemiluminescence.

Results:
A total of 486 patients were included in this study, and of these 249 had AIS (51%). RIC treatment was not associated with increased RBC maximal deformability (RIC: 0.549, Sham: 0.548, p=0.31), RBC NO (RIC 35.30 median fluorescence intensity[MFI], Sham: 34.98 MFI, p=0.89) or nitrite (RIC: 0.036 µM, Sham: 0.034 µM, p=0.38), but RIC treatment was associated with a significantly reduced aggregation pressure, and a slower erythrocyte aggregation rate (RIC: 323.76 Pascal, Sham: 352.74 Pascal, p=0.0113)

Conclusion:
Prehospital and in-hospital Remote ischemic conditioning significantly reduced erythrocyte aggregation rate in patients with acute ischemic stroke, while there was no change in red blood cell deformability, NO content or whole-blood nitrite levels.