Consequences of Cardiac Arrest: Brain Injury

心脏骤停的后果：脑损伤

• 批准号: 9980972
• 负责人: Romergryko Geocadin
• 金额: $ 55.04万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980972
• 关键词: Acute; Address; Behavioral; Biological Markers; Blood; Blood Pressure; Blood Vessels; Brain; Brain Injuries; Brain Ischemia; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Cerebrum; Clinical; Clinical Management; Diagnostic; Electroencephalography; Electrophysiology (science); Enhancement Technology; Epinephrine; Event; Foundations; Functional disorder; Goals; Guidelines; Heart Arrest; Histology; Homeostasis; Hyperemia; Hypoxia; Image; Impairment; Infusion procedures; Injury; Intervention; Knowledge; Link; Magnetic Resonance Imaging; Measures; Metabolic; Methods; Microscope; Monitor; Nervous System Physiology; Neurologic; Neurologic Deficit; Neurological outcome; Neuronal Injury; Nitroglycerin; Outcome; Oxygen; Perfusion; Pharmacological Treatment; Pharmacology; Phase; Physiologic pulse; Physiological; Protocols documentation; Recovery; Relaxation; Research; Resuscitation; Secondary to; Serum; Spin Labels; Survival Rate; Survivors; Syndrome; Techniques; Technology; Temperature; Therapeutic; Time; Translating; Ultrasonography; Work; base; blood pressure regulation; cerebral oxygenation; cerebrovascular; clinical practice; heart function; hemodynamics; hypoperfusion; improved; ischemic injury; microscopic imaging; multimodality; natural hypothermia; new technology; novel; novel therapeutics; perfusion imaging; pressure; programs; translational study

Cardiac arrest (CA) has devastating consequences, even with successful resuscitation survival rates are low and unfavorable outcomes in survivors are rampant which are almost uniformly secondary to brain injury. Our long-term research program studies the effects of global brain ischemia resulting from CA. In the first research phase, we developed and extensively validated measures of brain injury after CA. In the second phase, we embarked on demonstrating therapeutic solutions for major neurologic deficit. While high quality of cardiopulmonary resuscitation (CPR) has been shown to improve systemic perfusion, specific and validated guidelines related to post-CA brain perfusion and blood pressure management are non-existent (1-3). Our key hypothesis, laying the foundation for this proposal, is that brain function and neurologic outcome are dependent on the state of cerebrovascular autoregulation (CVAR). CVAR maintains a homeostatic cerebral blood flow (CBF) within a mean arterial pressure (MAP) range and protects the brain from injury during extremes of pressure and flow. After global hypoxic ischemic injury, CVAR is often impaired or absent. There is a need to develop direct measures of CVAR and validate it rigorously. Our central hypothesis is that individualizing MAP, CBF and hypothermia management as guided by CVAR monitoring will minimize brain injury and improve neurologic outcome. We have 5 aims. Aim 1: we will develop a miniature multicontrast microscope to continuously interrogate CVAR and COx throughout the post-CA recovery period. We acquired EEG measures, acute and late neuropathologic studies, early and long-term behavioral analyses as well as blood-based vascular biomarkers to objectively calibrate our CVAR (and COx) measures with neurologic outcomes. Aim 2, we will determine the relationship between CVAR dysfunction and post-CA whole brain injury as assessed by novel MRI based hemodynamic, oxygenation and metabolic biomarkers. Therefore, our aims 1 and 2 will enable us to characterize CVAR as a real time therapeutic guide as well as a prognosticator of outcome. For aims 3, 4 and 5, we will apply therapeutic maneuvers to restore and optimize CVAR as measured by the technologies developed in aims 1 and 2. Aim 3: we will focus on post-CPR MAP management and titrate MAP for optimal CVAR with epinephrine and nitroglycerine infusion to increase and decrease MAP respectively to improve neurologic outcomes. Aim 4: we study the effect CBF augmentation using low power therapeutic ultrasound. Aim5: We will focus on post-CA targeted temperature management therapy (TTM) and study the effects of titrating temperature on normalizing CVAR slope/shift. In summary, our proposal develops new technologies and therapies to address a critical knowledge gap in post-CPR CVAR management. We hope that our fundamental work will potentially translate into modified clinical practices for CA management in which, beyond rescuing the heart function, makes the brain the focus through CVAR based management of neurological function.

心脏骤停（CA）具有毁灭性的后果，即使成功复苏生存率也很低