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Rheoerythrocrine dysfunction in stroke and remote ischemic conditioning (REDS)

中风和远程缺血调节 (REDS) 中的红细胞分泌功能障碍

基本信息

批准号：
10565864
负责人：
DAVID C. HESS
金额：
$ 19.96万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10565864
关键词：
5&apos -AMP-activated protein kinase Accident and Emergency department Affect Ambulances Biological Markers Blinded Blood Blood Cells Blood Pressure Blood Vessels Blood flow Blood specimen Brain Cells Cerebrovascular Circulation Clinical Clinical Trials Controlled Clinical Trials Data Denmark Development Diameter Disabled Persons Disease Endothelial Cells Erythrocytes FDA approved Flow Cytometry Functional disorder Helicopter Hospitals Hypoxia Injury Ischemia Ischemic Stroke Limb structure Measures Microcirculation Mus NOS3 gene Nitrites Organ Outcome Oxygen Patients Pharmacodynamics Phase Plasma Play Pre-hospital setting Proteins Randomized Role SKIL gene Source Stroke Testing Therapeutic Traumatic Brain Injury Vasodilation Work acute stroke arm comorbidity conditioning endovascular thrombectomy functional improvement improved improved outcome indexing ischemic conditioning neuroprotection novel novel marker novel therapeutics outcome prediction pharmacodynamic biomarker post stroke pre-clinical response shear stress stroke clinical trials stroke patient stroke therapy stroke trials thrombolysis

项目摘要

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.

尽管血管内血栓切除术（ET）有效，但50%的患者在3个月时仍然残疾。需要溶栓和ET的辅助治疗，以提供“桥接神经保护”并改善侧枝。远程缺血调节（RIC），简单而安全的重复性血液膨胀-收缩在四肢上的压力（BP）袖带，改善急性中风的侧支血流。RIC目前正在一个大型一项在丹麦进行的1500例受试者的III期随机、假对照、院前急性卒中试验，RESIST 审判虽然一氧化氮合酶3（NOS 3）被认为仅限于内皮细胞，但现在已知红细胞血细胞（RBC）表达NOS 3，这种红细胞NOS 3（eryNOS 3）可能在微血管血流和缺血期间的器官保护。我们已经开发了两个假定的“流变- “红细胞分泌”生物标志物：红细胞变形性（ektacytometry）和erynOS 3（流式细胞术）。我们的假设 RBC变形性和erynOS 3是RIC的“药效学”生物标志物，改善急性卒中的结局。为了验证这一假设，我们将利用RESIST的临床试验平台生物标志物子研究的试验。我们的具体目标包括：目标1：确定RIC是否改善红细胞流变性与假手术相比，生物标志物（RBC变形性，增加活化的eryNOS 3）和/或增加血浆亚硝酸盐目的2：确定流变性红细胞分泌生物标志物是否与改善的短期（24小时）或长期 (90天mRS）临床结果。我们预期红细胞变形性和erynOS 3将成为红细胞凋亡的生物标志物。条件反应（药效学）和预测改善中风患者的临床结果。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Recycled Translation: Repurposing Drugs for Stroke.

DOI：
10.1007/s12975-022-01000-z
发表时间：
2022-12
期刊：
TRANSLATIONAL STROKE RESEARCH
影响因子：
6.9
作者：
Spellicy, Samantha E.;Hess, David C.
通讯作者：
Hess, David C.

Remote Ischemic Conditioning: Feasible and Potentially Beneficial for Ischemic Stroke.

DOI：
10.1001/jama.2022.13365
发表时间：
2022-08-16
期刊：
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
影响因子：
120.7
作者：
Hess, David C.;Blauenfeldt, Rolf A.;Andersen, Grethe
通讯作者：
Andersen, Grethe

Preclinical evaluation of circadian rhythm in ischemic stroke outcomes.

缺血性卒中结果中昼夜节律的临床前评估。

DOI：
发表时间：
2021
期刊：
Conditioning medicine
影响因子：
0
作者：
Kamat,PradipK;Khan,MohammadBadruzzaman;Wood,Kristofer;Siddiqui,Shahneela;Rudic,DanielR;Dhandapani,Krishnan;Waller,Jennifer;Hess,DavidC
通讯作者：
Hess,DavidC

The Immunomodulatory Capacity of Induced Pluripotent Stem Cells in the Post-stroke Environment.