Normobaric Hyperoxia in Acute Ischemic Stroke

急性缺血性中风的常压高氧症

基本信息

批准号：
7645683
负责人：
ANEESH B SINGHAL
金额：
$ 42.82万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-07 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7645683
关键词：
Acute Air Alteplase Animals Atmospheric Pressure Attenuated Biochemical Blood - brain barrier anatomy Blood Volume Brain Brain Ischemia Brain hemorrhage Breathing Cell Death Cerebrum Clinical Clinical Trials Coagulation Process Conflict (Psychology)Diffuse Diffusion Double-Blind Method Enrollment Failure Free Radicals Growth Hemorrhage Hour Human Hyperbaric Oxygen Hyperbaric Oxygenation Hyperoxia Hypoxia Incidence Infarction Injury Intention Ischemia Ischemic Stroke Lesion Magnetic Resonance Imaging Modeling Molecular Nervous System Physiology Neurologic Outcome Oxygen Oxygen Therapy Care Patients Perfusion Phase Randomized Reperfusion Therapy Research Personnel Risk Rodent Rodent Model Safety Stroke Techniques Testing Therapeutic Therapy Clinical Trials Time Tissues United States National Institutes of Health Work acute stroke base brain tissue cost effective therapy experience hemodynamics human data human study improved in vivo insight ischemic lesion neuroprotection novel prevent programs safety study

项目摘要

The wide availability, low cost, and multiple biochemical, molecular and hemodynamic effects of hyperoxia make it ideally suited as a neuroprotective strategy. In animal studies, and in a recent pilot human study, we have documented that breathing high-flow oxygen (normobaric hyperoxia therapy or NBO) during brain ischemia confers potent neuroprotection. The benefit of NBO appears to be transient, similar to that observed in prior hyperbaric oxygen studies. However, sustained benefit does occur if NBO-treated tissue is reperfused. We believe that today, with enhanced reperfusion rates from newer therapies such as tPA, and advances in MRI that allow serial assessment of tissue ischemia-reperfusion, there exists an exciting opportunity to assess whether NBO's transient tissue-salvaging effects can be converted (via induced or spontaneous reperfusion) into sustained benefit. By preventing early ischemic cell death, NBO may be a feasible strategy to extend the narrow time window for IV tissue plasminogen activator (tPA) therapy. In this proposal we aim to extend our preliminary work in a double-blind study enrolling 150 acute (<12 hours) ischemic stroke patients over 5 years. Patients will receive NBO or Room Air for 8 hours and will undergo serial clinical examinations and diffusion-perfusion MRI (DWI/PWI). Safety and efficacy of NBO will be determined in an 'intention to treat' statistical analysis of change in NIH stroke scale scores during and after therapy. The potential synergistic benefit of NBO with reperfusion will be assessed. We will also compare MRI ischemic lesion growth and hemorrhage rates, and perform novel voxel-based analyses of DWI and PWI parameters. In year 1 we will exclude tPA-treated patients and investigate the safety of NBO with tPA in an embolic (clot-based) rodent stroke model. If the combination appears safe in rodents, and if the year 1 human data raises no safety concerns, we will expand to include tPA-treated patients. Finally, we will conduct pathological and in-vivo MRI studies in rodent stroke models to investigate whether NBO can extend the tPA time window, and to investigate NBO's effects on cerebral hemodynamics. These studies are significant because they will comprehensively test the effects of oxygen in the ischemic brain. Breathing high-flow oxygen may prove to be a simple, practical, portable, and potentially cost-effective therapy that improves stroke outcomes, either independently or by extending the time window for IV tPA.

广泛的可用性，低成本以及多种生化，分子和血流动力学作用高氧使其理想地作为神经保护策略。在动物研究以及最近的飞行员研究，我们记录了在呼吸高流量氧（正常的高氧疗法或NBO）脑缺血赋予了有效的神经保护作用。 NBO的好处似乎是短暂的，类似在先前的高压氧研究中观察到。但是，如果经NBO处理的组织为重新填充。我们认为，今天，通过较新疗法（例如TPA）的再灌注率提高了，以及 MRI的进步，允许对组织缺血再灌注的连续评估，存在令人兴奋的有机会评估NBO是否可以转换NBO的瞬时组织腔化效应（通过诱导或自发再灌注）持续收益。通过预防早期缺血细胞死亡，NBO可能是可行的策略，以扩大IV组织纤溶酶原激活剂（TPA）治疗的狭窄时间窗口。在此提案中，我们旨在在招募150个急性的双盲研究中扩展我们的初步工作（<12 小时）缺血性中风患者超过5年。患者将接收NBO或房间空气8小时，将会经过串行临床检查和扩散 - 灌注MRI（DWI/PWI）。 NBO的安全性和功效将确定在“治疗”统计分析中，对NIH中风量表分数的变化和治疗后。将评估NBO对NBO的潜在协同益处。我们也会比较MRI缺血性病变生长和出血率，并进行基于体素的新分析 DWI和PWI参数。在第一年，我们将排除TPA治疗的患者并研究NBO的安全性在栓塞（基于凝块）啮齿动物中风模型中使用TPA。如果组合在啮齿动物中看起来很安全，如果第1年的人类数据没有引起安全问题，我们将扩展到包括经过TPA治疗的患者。最后，我们将在啮齿动物中风模型中进行病理和体内MRI研究，以研究NBO是否可以扩展TPA时间窗口，并研究NBO对脑血流动力学的影响。这些研究很重要，因为它们将全面测试氧在缺血性的影响脑。呼吸高流量氧气可能被证明是一种简单，实用，便携式且可能具有成本效益的可以独立或通过延长IV TPA的时间窗口来改善中风结果的治疗。