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）： 尽管美国每年有近 400,000 名患者心脏骤停，但过去 5 年来心肺复苏 (CPR) 后的平均存活率平均低于 5%。遗憾的是，手动标准心肺复苏本质上效率低下。最近的努力已转向通过机械辅助手段增加血液循环和逮捕后低温治疗（TH）来减少对大脑和心脏的缺血性损伤。自 50 年前首次描述胸外按压以来，一种促进重要器官血流正常化并同时允许进行心肺复苏 (CPR TH) 的方法可能对心脏骤停患者的神经系统完整生存产生最大影响。 在我们的拨款提案中，我们描述了第一个有利的结果，并建议需要对一种新的心肺复苏方法进行研究，该方法有可能用于所有心脏骤停的患者，并无论出现的节律如何，都能长时间维持心脏和大脑的活力。我们假设，通过结合使用硝普钠（SNP）（一种强效血管扩张剂）和机械心肺复苏辅助剂，我们可以有效地使心肺复苏产生的流向心脏和大脑的血流正常化。我们进一步假设药物诱导的皮肤血管舒张与高前向血流相结合将促进 CPR 内热交换和 TH。我们的试验数据表明，该提案的一个可实现的目标是最终表明，使用强效血管扩张剂结合促进心输出量和增加膈下血管阻力的非侵入性机械辅助剂来消除胸廓和脑血管收缩，将使心肺复苏期间重要器官的灌注正常化并维持。药物性皮肤血管舒张将加速与表面冷却的热交换，以便在恢复自主循环之前实现具有临床价值的 TH。我们提出的研究将：1.) 确定机械辅助剂和硝普钠 (SNP) 的最佳剂量的最佳组合，以优化心脏骤停后的血流和生存，2.) 证明 SNP CPR 在不同的心脏骤停模型中提供类似的益处，以及 3.) 证明 SNP CPR 可以提供即时有效的 CPR 内治疗性低温。 公共卫生相关性： 由于标准心肺复苏固有的无效性，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完整生存。我们提出了一种新方法，其中包括强效动脉扩张剂（硝普钠或 SNP）和非侵入性机械辅助装置，可增加心输出量并重新引导血流流向心脏和大脑。所提出的组合可以有效地用于在心肺复苏期间启动治疗性低温，初步研究已证明在所有复苏相关结果中与标准心肺复苏相比具有独特的优势。