# Rheoerythrocrine dysfunction in stroke and remote ischemic conditioning (REDS)

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2022 · $248,320

## Abstract

Despite the efficacy of endovascular thrombectomy (ET), 50% of the patients remain disabled at 3 months.
Adjunctive therapies to thrombolysis and ET are needed that provide “bridging neuroprotection” and improve
collaterals. Remote ischemic conditioning (RIC), the simple and safe repetitive inflation-deflation of a blood
pressure (BP) cuff on the limbs, improves collateral blood flow in acute stroke. RIC is now being tested in a large
phase III randomized, sham-controlled, prehospital acute stroke trial of 1500 subjects in Denmark, the RESIST
trial. While nitric oxide synthase 3 (NOS3) was thought restricted to endothelial cells, it is now known that red
blood cells (RBCs) express NOS3 and that this erythrocyte NOS3 (eryNOS3) may play a critical role in
microvascular blood flow and organ protection during ischemia. We have developed two putative “rheo-
erythocrine” biomarkers: RBC deformability by ektacytometry and eryNOS3 by flow cytometry. Our hypothesis
is that RBC deformability and eryNOS3 are “pharmacodynamic” biomarkers of RIC and will be related to
improved outcome in acute stroke. To test this hypothesis we will utilize the clinical trial platform of the RESIST
trial for a biomarker substudy. Our specific aims include: Aim 1: Determine if RIC improves rheoerythrocrine
biomarkers (RBC deformability, increases activated eryNOS3) and/or increases plasma nitrite compared to sham
RIC .Aim 2: Determine if rheo-erythrocrine biomarkers are related to improved short term (24 hr) or long term
(90 day mRS) clinical outcome. We expect that RBC deformability and eryNOS3 will be biomarkers of the
conditioning response (pharmacodynamic) and predictive of improved clinical outcome in stroke patients.

## Key facts

- **NIH application ID:** 10335203
- **Project number:** 5R01NS112511-03
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** DAVID C. HESS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $248,320
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335203

## Citation

> US National Institutes of Health, RePORTER application 10335203, Rheoerythrocrine dysfunction in stroke and remote ischemic conditioning (REDS) (5R01NS112511-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10335203. Licensed CC0.

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