Sodium nitroprusside and mechanical CPR adjuncts for cardio-cerebral resuscitatio

描述（由申请人提供）： 尽管在美国每年有近40万患者遭受心脏骤停，但在过去的50年中，心脏复苏（CPR）后的平均存活率平均<5%。遗憾的是，手动标准CPR本质上是低效的。最近的努力已经转移到通过机械通气和停搏后治疗性低温（TH）增加循环来减少对大脑和心脏的缺血性损伤。自50年前首次描述胸部按压以来，一种促进重要器官血流正常化并同时允许CPR内TH的方法可能对心脏骤停中的神经完整存活率产生最大影响。 在我们的拨款申请中，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，这种方法有可能用于所有心脏骤停患者，并在长时间内维持心脏和大脑的活力，而不管呈现的节律如何。我们假设，通过使用硝普钠（SNP），一种有效的血管扩张剂和机械心肺复苏术的组合，我们可以有效地使心肺复苏术产生的流向心脏和大脑的血流正常化。我们进一步假设，心肺复苏术诱导的皮肤血管舒张，结合高前向血流，将促进CPR内热交换和TH。我们的试验数据表明，该提议的可实现目标是最终表明，用有效的血管扩张剂结合促进心输出量和增加动脉下血管阻力的非侵入性机械刺激消除胸和脑血管收缩，将使CPR期间的重要器官灌注正常化并维持重要器官灌注。药理学皮肤血管舒张将加速与表面冷却的热交换，使得在返回自主循环之前可以实现具有临床价值的TH。我们的研究将：（1）确定机械除颤器的最佳组合和硝普钠（SNP）的最佳剂量，以优化心脏骤停后的血流和存活率，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可以提供即时和有效的CPR内治疗性低温。 公共卫生相关性： 由于标准CPR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系统完整的生存。我们提出了一种新的方法，包括一种有效的动脉扩张剂（硝普钠或SNP）和非侵入性机械扩张剂，增加心输出量并将血流重新导向心脏和大脑。所提出的组合可以有效地用于在CPR期间开始治疗性低温，并且初步研究已经证明了与标准CPR相比在所有复苏相关结果中的独特优势。

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.