rLOAD: Loading of Aspirin and Clopidogrel in Rabbit Model of Ischemic Stroke

rLOAD：缺血性中风兔模型中阿司匹林和氯吡格雷的负荷

• 批准号: 7613094
• 负责人: Dawn Matherne Meyer
• 金额: $ 4.1万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-20 至 2011-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7613094
• 关键词: Acute; Affect; Alteplase; Alternative Therapies; Anesthetics; Animal Model; Animals; Appendix; Aspirin; Behavior; Behavioral; Blinded; Blood Platelets; Blood Vessels; Brain Injuries; Cardiac; Caregivers; Caring; Clinical; Clinical Trials; Coagulation Process; Community Healthcare; Condition; Conscious; Data; Devices; Disease; Dose; Effectiveness of Interventions; Etiology; Evaluation; Excision; Facilities and Administrative Costs; Foreign Bodies; Foundations; Health care facility; Hemorrhage; Hour; Human; Human Characteristics; Infarction; Intervention; Intravenous; Ischemia; Ischemic Stroke; Knowledge; Left; Life; Measurement; Mechanics; Medical Device; Methodology; Methods; Modeling; Nature; Neuroanatomy; Neurologic; Neurology; New Zealand; Oryctolagus cuniculus; Outcome; Patients; Physiological; Platelet aggregation; Postdoctoral Fellow; Purpose; Randomized; Rate; Research; Research Project Grants; Resistance; Retrieval; Safety; Score; Standards of Weights and Measures; Statistically Significant; Stroke; Symptoms; Tenecteplase; Testing; Therapeutic Embolization; Time; Translating; Translations; Unconscious Personality Factor; Unconscious State; United States; United States Food and Drug Administration; acute stroke; clopidogrel; concept; disability; improved; neuroprotection; novel; pre-clinical; stroke therapy

DESCRIPTION (provided by applicant): Acute stroke affects over 700,000 people annually in the United States(US).(1) Currently, the only FDA approved treatment for acute ischemic stroke is intravenous recombinant tissue plasminogen activator (rt-PA) administered within three hours of stroke symptom onset.(2) Only 3-8% of all stroke patients in the US are treated with rt-PA because most present to healthcare facilities beyond the three hour treatment window.1 Alternative therapies must be researched to provide treatment options for the hundreds of thousands of stroke patients for which no approved acute therapy exists. Acute antiplatelet loading is utilized in the treatment of cardiac vascular occlusive disease. The use of an animal model to test anti platelet loading as a stroke intervention will provide a rigorous foundation for translation into human clinical trials. The purpose of this study is to: 1) determine the effect of standard aspirin treatment, low anti platelet loading, and high antiplatelet loading on time to platelet aggregation in the rabbit small clot embolic model; 2) to determine the efficacy of standard aspirin treatment, low anti platelet loading, and high antiplatelet loading on reduction of infarct volume in the rabbit small clot embolic model (RSCEM); and 3) to compare neurologic behavior outcomes in the standard aspirin treatment, low anti platelet loading, and high anti platelet loading group in the rabbit small clot embolic model. White, New Zealand rabbits will be randomized to standard aspirin treatment, low antiplatelet loading dose, or high antiplatelet loading dose. A clot (embolization) will be introduced into each animal via the RSCEM methodology. Rabbits will receive treatment according to randomization assignment two hours post-embolization. Behavioral outcomes will be assessed at hour 0,5,8,24, and 48 post-embolization via the rabbit clinical rating scale.(54) After hour 48, animals will be sacrificed and hemorrhage rate and infarct volume will be compared. The outcomes of the proposed research project will serve the 700,000 people who suffer acute stroke each year. A gap in the knowledge exists regarding novel treatment of ischemic stroke beyond the thrombolytic window with anti platelet loading. Filling this gap may result in a decrease in stroke burden to the healthcare community and stroke victims and their caregivers. In addition, assessment for maximal antiplatelet dosing that is safe is critical to the treatment of many aspirin and c1opidogrel resistant patients. This animal model research will translate into the support of a new stroke therapy that will limit brain injury, extend healthy life, and reduce disability from ischemic stroke.

描述（由申请人提供）：急性中风每年在美国（美国）影响超过70万人。（1）目前，唯一的FDA批准治疗急性缺血性中风的治疗方法是静脉内重组组织纤溶酶原激活因子（RT-PA）在三个小时内施加了三个小时内的中风症状。除三个小时的治疗窗口以外的设施。1必须研究替代疗法，以为数十万中风患者提供治疗选择，而该患者不存在批准的急性疗法。 急性抗血小板负荷用于治疗心脏血管闭塞性疾病。使用动物模型来测试抗血小板负荷作为中风干预措施，将为转化为人类临床试验提供严格的基础。这项研究的目的是：1）确定标准阿司匹林治疗，低抗血小板负荷和高抗血小板加载的影响，时间是兔子小凝块栓塞模型中血小板聚集的时间； 2）确定标准阿司匹林治疗的功效，低抗血小板负荷和高抗血小板负荷在兔子小凝块栓塞模型（RSCEM）中减少梗塞体积的效果； 3）比较标准阿司匹林治疗中的神经系统行为结果，低抗血小板负荷和兔子小凝块栓塞模型中的高抗血小板加载组。白色，新西兰兔子将被随机分为标准的阿司匹林治疗，低抗血小板负荷剂量或高抗血小板加载剂量。通过RSCEM方法，将引入每种动物的凝块（栓塞）。兔子将在栓塞后两个小时根据随机分配接受治疗。行为结果将在0,5,8,24小时评估，并通过兔临床评级量表进行48个启动后。（54）48小时后，将处死动物，并将其出血率和梗塞体积进行比较。 拟议的研究项目的结果将为每年急性中风的70万人提供服务。知识的差距是关于抗血小板负荷的溶栓窗口以外的缺血性中风的新型治疗的差距。填补这一空白可能会导致医疗保健社区和中风受害者及其护理人员的中风负担减轻。此外，对安全的最大抗血小板剂量的评估对于治疗许多阿司匹林和C1Opidogrel耐药患者至关重要。这项动物模型研究将转化为一种新的中风疗法的支持，该疗法将限制脑损伤，延长健康的生命并减少缺血性中风的残疾。