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

• 批准号: 10335203
• 负责人: DAVID C. HESS
• 金额: $ 24.83万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10335203
• 关键词: 5' -AMP-activated protein kinase; Accident and Emergency department; Affect; Ambulances; Biological Markers; Blinded; Blood; Blood Cells; Blood Pressure; Blood flow; Blood specimen; Brain; Caliber; Cells; Cerebrovascular Circulation; Clinical; Clinical Trials; Controlled Clinical Trials; Data; Denmark; Development; 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; Nitrogen Dioxide; 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; improved; improved functioning; 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

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。