Non-invasive Extra-Corporeal Circulator for Prolonged Resuscitation

描述（申请人提供）：基于新发现的在心肺复苏术中增强循环的机制，SBIR第一阶段应用的目标是开发一种全面的、新颖的非侵入性体外自动循环辅助装置，用于在心脏骤停期间使血流正常化，并提供长时间的充分循环，从而将患者运送到医院，在那里他们可以接受更明确的治疗。该器械设计用于在CPR过程中利用胸内泵机制提供足够的前向血流，重新充盈心脏以维持正常血压，降低颅内压，并通过使用同步下肢反搏进一步增加静脉回流并将舒张期血流引导至心脏和大脑。该新方法还旨在减少或消除对潜在有害的外源性血管加压药治疗的需求。为了提供长期有效的复苏，三项核心技术将结合到一个设备中。它们是：i）使用气动胸骨加压装置的主动加压减压（ACD）CPR。ii）提供胸内压力调节的装置，其与提供正压通气的装置耦合。iii）下肢反搏（LECP），其具有连接到ACD CPR设备的电驱动冲击裤状设备。在胸部按压-减压循环的减压阶段，LECP将同步充气和压缩下肢。这3项核心技术将通过电子方式协调和控制，以增强心脏前负荷，使血流流向大脑，并最大限度地减少颅内对脑灌注的阻力。这种非侵入性机制的独特组合有望提供一种手段，以提供延长的正常血液循环，直到可以以受控的方式提供最终护理，如冠状动脉血运重建。这项研究建议的三个具体目标是：1）设计和构建用于治疗心脏骤停的原型非侵入性循环支持设备，以向心脏和大脑提供正常循环，2）在动物模型中协调和测试CPR设备系统部件的不同配置，以最大化重要器官灌注压力和血流，和3）证明了使用新型CPR装置将导致正常循环持续至少一小时的延长CPR、有效除颤和24小时神经学完整存活的概念证明。来自申办者实验室和其他实验室的数据表明，如果在CPR和复苏后护理期间优化心脏和大脑的循环，延长CPR是可行的。拟议的设备开发和拟议的范式转变有望为我们的理解和最终的临床方法提供根本性的变化，为绝大多数患者，无论是年轻人还是老年人，他们无法用目前的基本和先进的生命支持技术复苏。公共卫生相关性：该SBIR第1阶段申请的目标是进一步开发一种全面的新型体外循环辅助器械，以在心脏骤停期间使血流正常化，并在较长时间内以无创方式提供充足的循环，从而将患者运送到医院，在那里他们可以接受更明确的治疗。该器械设计用于在CPR期间利用胸内泵机制提供足够的前向血流，重新充盈心脏以维持正常血压，并在无外源性血管加压剂治疗的情况下降低颅内压。为了提供长期有效的复苏，三项核心技术将结合到一个设备中。它们是：i）使用气动胸骨压缩装置的主动压缩减压（ACD）CPR。ii）提供胸内压力调节的装置，其与提供正压通气的装置耦合。iii）下肢反搏（LECP），其具有连接到ACD CPR设备的电驱动冲击裤状设备。在胸部按压-减压周期的减压阶段，LECP将同步充气和压缩下肢。这3项核心技术将通过电子方式协调和控制，以增强心脏前负荷，使血流流向大脑，并最大限度地减少颅内对脑灌注的阻力。这种非侵入性机制的独特组合有望提供一种手段，以提供延长的正常血液循环，直到可以以受控的方式提供最终护理，如冠状动脉血运重建。如果这个项目成功，新的复苏系统有可能使美国每年发生在医院外的40万心脏猝死患者中的大约5万人复苏。这一估计没有考虑到每年在医院发生的心脏性猝死患者的数量几乎相等。

DESCRIPTION (provided by applicant): Based upon newly discovered mechanisms to enhance circulation during CPR, the goal of this SBIR phase 1 application is to develop a comprehensive and novel non-invasive extracorporeal automated circulatory assist device to normalize blood flow during cardiac arrest and to provide adequate circulation for prolonged periods of time allowing for transport of patients to the hospital where they can receive more definite therapies. The device is designed to harness both the intrathoracic pump mechanism during CPR to provide sufficient forward flow, to refill the heart to maintain normal blood pressures, to lower intracranial pressures, and to further augment venous return and direct diastolic flow to the heart and brain by using synchronized lower extremity couterpulsation. The novel approach is also designed to reduce or eliminate the need for potentially harmful exogenous vasopressor therapies. To provide prolonged effective prolonged resuscitation, three core technologies will be combined into one device. They are: i) Active compression decompression (ACD) CPR with a pneumatic sternal compression device. ii) A means to provide intrathoracic pressure regulation coupled with a means to provide positive pressure ventilation. iii) Lower extremity counterpulsations (LECP) with a pneumatically driven shock-trousers-like device linked to the ACD CPR device. The LECP will be synchronized to inflate and compress the lower limbs during the decompression phase of the chest compression - decompression cycle. These 3 core technologies will be coordinated and controlled electronically to enhance cardiac preload, forward blood flow to the brain, and minimize intracranial resistance to cerebral perfusion. This unique combination of non-invasive mechanisms promises to provide a means to provide prolonged normal blood circulation until definitive care, such as coronary revascularization, can be provided in a controlled manner. The three specific aims of this research proposal are: 1) design and build a prototype non-invasive circulatory support device for the treatment of cardiac arrest to provide normal circulation to the heart and brain, 2) coordinate and test the different configurations of the CPR device system components in an animal model to maximize vital organ perfusion pressures and blood flow, and 3) demonstrate proof of concept that use of the novel CPR device will result in normal circulation for at least one hour of prolonged CPR, effective defibrillation, and 24-hour neurological-intact survival. Data from the sponsor's laboratory and from other laboratories have shown that prolonged CPR is feasible if circulation to the heart and brain during CPR and post-resuscitation care are optimized. The proposed device development and the proposed paradigm shift promises to provide a fundamental change in our understanding and ultimately clinical approach for the vast majority of patients, both young and old, who cannot be resuscitated with current basic and advanced life support techniques. PUBLIC HEALTH RELEVANCE: The goal of this SBIR phase 1 application is to further develop a comprehensive and novel extracorporeal circulatory assist device to normalize blood flow during cardiac arrest and to non- invasively provide adequate circulation for prolonged periods of time allowing for transport of patients to the hospital where they can receive more definite therapies. The device is designed to harness the intrathoracic pump mechanism during CPR to provide sufficient forward flow, to refill the heart to maintain normal blood pressures, and to lower intracranial pressures in the absence of exogenous vasopressor therapy. To provide prolonged effective prolonged resuscitation, three core technologies will be combined into one device. They are: i) Active compression decompression (ACD) CPR with a pneumatic sternal compression device. ii) A means to provide intrathoracic pressure regulation coupled with a means to provide positive pressure ventilation. iii) Lower extremity counterpulsations (LECP) with a pneumatically driven shock-trousers-like device linked to the ACD CPR device. The LECP will be synchronized to inflate and compress the lower limbs during the decompression phase of the chest compression - decompression cycle. These 3 core technologies will be coordinated and controlled electronically to enhance cardiac preload, forward blood flow to the brain, and minimize intracranial resistance to cerebral perfusion. This unique combination of non-invasive mechanisms promises to provide a means to provide prolonged normal blood circulation until definitive care, such as coronary revascularization, can be provided in a controlled manner. If this program is successful, the new resuscitation system has the potential to resuscitate approximately 50,000 more patients of the 400,000 sudden cardiac deaths that occur outside the hospital each year in the United States. This estimation does not take into account a nearly equal number of patients with sudden cardiac death that occur in-hospital each year.