Sodium nitroprusside and mechanical CPR adjuncts for cardio-cerebral resuscitatio

硝普钠和机械心肺复苏辅助剂用于心脑复苏

• 批准号: 8153318
• 负责人: Demetris Yannopoulos
• 金额: $ 59.76万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-25 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8153318
• 关键词: Animal Model; Applications Grants; Blood; Blood Circulation; Blood flow; Brain; Cardiac; Cardiac Output; Cardiopulmonary Resuscitation; Cerebral Ischemia; Cerebrum; Cessation of life; Chest; Clinical Trials; Combined Modality Therapy; Coronary Occlusions; Cutaneous; Data; Development; Devices; Dilator; Disodium Salt Nitroprusside; Dose; Electric Countershock; Etiology; Family suidae; Goals; Hand; Heart; Heart Arrest; Heating; Hospitals; Hour; Human; Manuals; Mechanics; Methodology; Methods; Modeling; Nervous System Physiology; Neurologic; Neurological outcome; Organ; Outcome; Patients; Perfusion; Pharmaceutical Preparations; Research; Resuscitation; Secondary to; Surface; Survival Rate; Survivors; Temperature; Testing; Therapeutic; Translating; Translations; United States; Vascular resistance; Vasodilation; Vasodilator Agents; Ventricular Fibrillation; base; clinical effect; improved; innovation; natural hypothermia; novel; pressure; prevent; protective effect; vasoconstriction

DESCRIPTION (provided by applicant): Although almost 400,000 patients suffer cardiac arrest each year in the United States, average survival rates following Cardiopulmonary Resuscitation (CPR) have averaged <5% for the last 5 decades. Regrettably, manual standard CPR is inherently inefficient. Recent efforts have been shifted to reduce the ischemic damage to the brain and heart by increasing circulation with mechanical adjuncts and post arrest therapeutic hypothermia (TH). A method which promotes normalization of vital organ blood flow and simultaneously allows for intra-CPR TH could have the greatest impact on neurologically intact survival in cardiac arrest since the first description of chest compressions 50 years ago. In our grant proposal we describe the first favorable results and suggest research that needs to be performed on a new method of CPR with the potential to be used in all patients with cardiac arrest and maintain heart and brain viability for prolonged periods regardless of the presenting rhythm. We hypothesize that by using a combination of sodium nitroprusside (SNP), a potent vasodilator, and mechanical CPR adjuncts we can effectively normalize CPR-generated blood flow to the heart and brain. We further hypothesize that the pharmacologically induced cutaneous vasodilatation, combined with high forward blood flow, will facilitate intra- CPR heat exchange and TH. Our pilot data indicate that an achievable goal of this proposal is to conclusively show that elimination of thoracic and cerebral vasoconstriction with a potent vasodilator combined with non- invasive mechanical adjuncts that promote cardiac output and increase sub-diaphragmatic vascular resistance, will normalize and maintain vital organ perfusion during CPR. The pharmacological cutaneous vasodilatation will expedite heat exchange with surface cooling so that clinically valuable TH can be achieved before return to spontaneous circulation. Our proposed research will: 1.) identify the optimal combination of mechanical adjuncts and the optimal dose of sodium nitroprusside (SNP) to optimize flow and survival after cardiac arrest, 2.) demonstrate that SNP CPR offers similar benefits in different cardiac arrest models, and 3.) demonstrate that SNP CPR can provide immediate and effective intra-CPR therapeutic hypothermia. PUBLIC HEALTH RELEVANCE: Due to inherent ineffectiveness of standard CPR a new more efficient method is needed to significantly improve resuscitation outcomes and long term neurological intact survival. We propose a new method which includes a potent arterial dilator (sodium nitroprusside or SNP) and non invasive mechanical adjuncts that increase cardiac output and re-direct flow to the heart and brain. The proposed combination can efficiently be used for initiation of therapeutic hypothermia during CPR and preliminary studies have demonstrated a distinctive advantage compared to standard CPR in all resuscitation related outcomes.

描述（由申请人提供）： 尽管在美国，每年近40万名患者每年遭受心脏骤停，但在过去的5年中，心肺复苏（CPR）后的平均生存率平均<5％。遗憾的是，手动标准CPR本质上效率低下。最近的努力已转移，以减少与机械辅助和停滞后治疗性低温（TH）的循环循环，以减少对大脑和心脏的缺血性损害。自从50年前对胸部压缩的第一个描述以来，一种促进重要器官血流并同时允许对神经系统完整生存的影响的方法，可能对神经学完整的生存产生最大的影响。 在我们的赠款建议中，我们描述了第一个有利的结果，并提出了需要对新的CPR方法进行的研究，该研究有可能在所有心脏骤停患者中使用，并长时间保持心脏和脑生存能力，无论其节奏如何。我们假设，通过使用硝普钠（SNP）的组合，有效的血管扩张剂和机械CPR辅助，我们可以有效地使CPR产生的血液流向心脏和大脑。我们进一步假设，药理学诱导的皮肤血管舒张，结合高前血流，将有助于内部热量交换和Th。我们的试点数据表明，该提案的一个可实现的目标是最终表明，消除胸腔和脑血管收缩，并具有有效的血管扩张剂与非侵入性的机械辅助作用相结合，可促进心脏输出并增加副脑血管抗性，并增加脑部血管抗性，将在CPR期间标准化并维持重要的CPR机构灌注。药理学皮肤血管舒张将加快表面冷却的热量交换，以便在返回自发循环之前可以实现临床上有价值的TH。我们拟议的研究将：1。）确定机械辅助剂和硝普钠（SNP）最佳剂量的最佳组合，以优化心脏骤停后的流量和生存，2。）证明SNP CPR在不同的心脏骤停模型中提供了类似的好处，并且3.）证明SNP CPR可以提供直接和有效的内经鞘内疗法，并提供了有效的内经疗法。 公共卫生相关性： 由于标准CPR的固有无效性，需要一种新的更有效的方法来显着改善复苏结果和长期神经系统完整的生存。我们提出了一种新方法，其中包括有效的动脉扩张剂（硝普钠或SNP）和非侵入性机械辅助物，从而增加心脏输出并将流动转向心脏和大脑。在CPR期间，所提出的组合可以有效地用于启动治疗性体温过低，并且初步研究表明，与标准CPR相比，在所有复苏相关的结果中都具有独特的优势。