Neuroprotection After Cardiac Arrest

心脏骤停后的神经保护

• 批准号: 6817717
• 负责人: GARY M FISKUM
• 金额: $ 35.35万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6817717
• 关键词: brain injury; cardiopulmonary resuscitation; cell death; cerebral ischemia /hypoxia; dogs; heart arrest; histopathology; laboratory rat; neuropathology; neuroprotectants; outcomes research; oxidative stress; oximetry; oxygen tension; statistics /biometry

DESCRIPTION (provided by applicant):Comparisons of pre-lethal neurochemical alterations to neurologic outcome and neuropathology following cardiac arrest (CA) and resuscitation in animals using hyperoxic and normoxic ventilation strongly implicate early, oxidative modification to mitochrondial proteins and associated metabolic dysfunction in the etiology of delayed neural cell death and permanent brain injury. To expedite progress in improving neurologic outcome following human CA, we propose a change in standard resuscitative protocols that dramatically lowers the concentration of inspired 02 (Fi02) to a level that sufficiently oxygenates the brain and other tissues but that minimizes oxidative stress, cell death, and neurologic impairment. Our specific aims test the hypothesis that neuronal cell death and both short- and long-term neurologic impairment following CA and resuscitation are minimized by maintaining normal post-ischemic PaO2, as guided by oximetry-based measurements of hemoglobin 02 saturation (SpO2) that are practical for use in the field. Aim 1. Compare neurologic outcome following canine cardiac arrest and resuscitation using:* Hyperoxic Resuscitation - 100% FiO2 for 1 hr then adjust FiO2 to maintain normal PaO2 * Normoxic Resuscitation - 21% FiO2 for 1 hr then adjust FiO2 to maintain normal PaO2 * Oximetry-Based Resuscitation - Adjust FiO2 to maintain SpO2 at 94% to 96% *Aim 2. Establish relationships between resuscitative FiO2 and neuronal cell death using the canine model and three resuscitation protocols. Aim 3. Extend the results obtained with the short-term canine CA model using a transient global cerebral ischemia model with long-term outcome measures performed on mature and aged rats. We will compare both neurologic outcome and neuronal cell death using different protocols in a clinically very relevant canine model of cardiac arrest. In addition, a rat model of transient global cerebral ischemia is utilized to measure long-term outcome and to test different protocols on aged animals, representing the typical CA patient age-group. Within the first two - three years of this project, our results could be used to design clinical trials to improve neurologic outcome following cardiac arrest and resuscitation. With over 250,000 cardiac arrest victims resuscitated each year in the U.S. alone, and over half of these suffering from neurological morbidity and mortality, the potential impact of the proposed translational research project is highly significant.

DESCRIPTION (provided by applicant):Comparisons of pre-lethal neurochemical alterations to neurologic outcome and neuropathology following cardiac arrest (CA) and resuscitation in animals using hyperoxic and normoxic ventilation strongly implicate early, oxidative modification to mitochrondial proteins and associated metabolic dysfunction in the etiology of delayed neural cell death and permanent brain injury.为了加快人类CA后改善神经系统结局的进展，我们提出了标准复苏方案的变化，这些方案将大幅度地降低了受启发的02（FI02）的浓度至一个充分氧化大脑和其他组织的水平，但可以最大程度地氧化氧化应激，细胞死亡，细胞死亡，神经系统损害。我们的具体目的检验了CA和复苏后神经元细胞死亡以及短期和长期神经系统障碍的假设，通过维持正常的缺血后PAO2来最大程度地降低，这是由基于氧仪的血红蛋白02饱和度（SPO2）的测量所指导的，这些测量可用于现场。目的1。使用以下方式比较神经系统骤停和复苏： *高氧复苏-100％FIO2持续1小时，然后调整FIO2以保持正常的PAO2 *差异固定复苏-21％FIO2固定1小时，1小时，然后调整FIO2，然后调整FiO2以维持正常的PAO2 *基于Oximetry的ResusiTry SPOSS SPOSS SPO 2，以维持SPO 2的2.6％的fio2 fio2 fio2 94使用犬模型和三种复苏方案的复苏FIO2和神经元细胞死亡。 AIM 3。使用短期全局脑缺血模型扩展了用短期犬CA模型获得的结果，该模型具有长期的成熟和老年大鼠进行的长期结局指标。我们将使用临床上非常相关的心脏骤停模型中的不同方案来比较神经系统结局和神经元细胞死亡。此外，将瞬时全球脑缺血的大鼠模型用于测量长期结果并测试对老年动物的不同方案，代表典型的CA患者年龄段。在该项目的前两年中，我们的结果可用于设计临床试验，以改善心脏骤停和复苏后的神经系统效果。仅在美国，每年有超过250,000名心脏骤停的受害者复苏，其中一半以上患有神经系统发病率和死亡率，拟议的翻译研究项目的潜在影响非常重要。