Sodium nitroprusside and mechanical CPR adjuncts for cardio-cerebral resuscitatio

描述(由申请人提供)： 尽管美国每年有近40万名患者心脏骤停，但在过去的50年里，心肺复苏(CPR)后的平均存活率一直保持在5%。遗憾的是，人工标准心肺复苏术天生效率低下。最近的努力已经转移到减少脑和心脏的缺血性损伤，通过增加机械辅助的循环和停搏后的治疗低温(TH)。一种促进重要器官血流正常化并同时允许心内复苏的方法，可能会对自50年前首次描述胸部按压以来心脏骤停患者的神经完整存活率产生最大影响。在我们的拨款提案中，我们描述了第一个有利的结果，并建议对一种新的CPR方法进行研究，这种方法有可能用于所有心脏骤停患者，并在较长时间内保持心脏和大脑的存活，而不考虑呈现的节奏。我们假设，通过结合使用硝普钠(SNP)，一种有效的血管扩张剂，以及机械CPR辅助设备，我们可以有效地使CPR产生的流向心脏和大脑的血流量正常化。我们进一步假设，药物诱导的皮肤血管扩张，结合高前向血流，将促进心肺复苏期间的热量交换和心脏复苏术。我们的初步数据表明，这项建议的一个可实现的目标是最终表明，在CPR期间，使用有效的血管扩张剂结合非侵入性机械附件来增加心输出量和增加膈下血管阻力来消除胸腔和脑血管收缩，将使重要器官的血流正常并保持正常。药理作用下的皮肤血管扩张可通过体表降温促进热交换，从而在恢复自主循环前实现有临床价值的治疗。我们提出的研究将：1.)确定机械辅助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。证明SNP CPR在不同的心脏骤停模型中提供类似的好处，以及3.)证明SNP CPR可提供即刻有效的心肺复苏内治疗性低温。 公共卫生相关性： 由于标准CPR固有的无效，需要一种新的更有效的方法来显着改善复苏结果和长期完整的神经生存。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)和非侵入性机械附件，以增加心输出量并将血流重新定向到心脏和大脑。建议的组合可以有效地用于CPR期间的治疗性低温治疗，初步研究表明，与标准CPR相比，在所有与复苏相关的结果中，该组合具有明显的优势。

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.