Effects of a Pulse Induced by a Constant-Flow Total Cardiac Replacement Device

描述（由申请人提供）：一个简单，安全，可靠的机械替代失败的人类心脏将大大影响医疗保健。在过去的四十年里，已经花费了大量的努力来开发心脏替代装置（CRD），但是技术障碍一直是令人望而却步的。在过去的7年中，恒流（CF）旋转血泵的推出彻底改变了心脏支持领域。这些泵比它们的脉动前辈更小，更节能，生产成本更低，而且它们没有阀门和柔性膜，使它们不受机械磨损的影响。超过1，000名患者接受了CF泵治疗;首批植入的此类泵之一在6年多后功能良好。拟议BRP项目的目标是证明由两个集成CF（HeartMate III）旋转泵组成的下一代CRD可以提供足够的肺循环和体循环，以满足生理需求。本项目的具体目标是（1）使用工程和体内实验相结合的方法完善和改进用于全心脏置换术的CRD，使该器械可使小牛在植入后茁壮成长长达3个月，并比较在恒定流中使用CRD的小牛的生理学（2）在肺和其他器官的微血管水平上观察无脉和减脉灌注的效果;和（3）评价CRD植入小牛的运动能力和CRD在运动期间对增加的代谢需求作出反应的能力。这项研究应该提供必要的证据，将全球CRD开发的努力从容量置换转移到CF技术，并将加速“终末期心力衰竭的管理”从未满足的临床需求列表中划掉的那一天。该领域的先驱、创新人才、经验丰富的机构和为此工作提出的资源的集合，以及参与机构之间的长期合作，最终促成了开创性的临床试验，使该BRP团队能够成功实现其既定目标。公共卫生相关性：心力衰竭是美国过早死亡的主要原因。一种简单、安全、可靠的机械替代品来替代衰竭的人类心脏，将对医疗保健产生巨大的影响。为此，该项目的目标是开发一种使用两个恒流血泵的永久性心脏置换装置（CRD），该装置比其脉动式前辈更小，更有效，更可靠，更便宜。

DESCRIPTION (provided by applicant): A simple, safe, reliable mechanical replacement for the failing human heart would dramatically impact health care. Over the past four decades, substantial effort has been expended to develop a cardiac replacement device (CRD), but technical hurdles have been prohibitive. The introduction of the constant-flow (CF) rotary blood pump over the last 7 years has revolutionized the field of cardiac support. These pumps are smaller, more energy efficient, and less expensive to produce than their pulsatile predecessors, and their lack of valves and flexible membranes makes them impervious to mechanical wear. More than 1,000 patients have been treated with CF pumps; one of the first such pumps to be implanted functions well more than 6 years later. The goal of the proposed BRP project is to show that a next-generation CRD comprising two integrated CF (HeartMate III) rotary pumps can provide adequate pulmonary and systemic circulation to meet physiologic demands. The specific aims of this project are (1) to refine and improve the CRD for total cardiac replacement using combined engineering and in vivo experiments, such that the device allows calves to thrive for up to 3 months after implantation, and to compare the physiology of the calves using the CRD in constant-flow (pulseless) mode or actuated to impart a physiologic pulse pressure at 40 pulses/min; (2) to observe the effects of pulseless and reduced-pulse perfusion at the microvascular level in the lungs and other organs; and (3) to evaluate the exercise capacity of CRD-implanted calves and the ability of the CRD to respond to increased metabolic demands during exercise. This study should provide the necessary evidence to shift global efforts at CRD development from volume-displacement to CF technology and will hasten the day when "management of end-stage heart failure" can be crossed off the list of unmet clinical needs. The assemblage of pioneers in the field, innovative talent, experienced institutions, and resources proposed for this work-as well as the longstanding collaboration between the participating institutions that has culminated in pioneering clinical trials-uniquely positions this BRP team t successfully achieve its stated goals. PUBLIC HEALTH RELEVANCE: Heart failure is the leading cause of premature death in the United States. A simple, safe, reliable mechanical replacement for the failing human heart would have a dramatic impact on health care. To that end, the goal of this project is to develop a permanent cardiac replacement device (CRD) using two constant-flow blood pumps, which are smaller, more efficient, more reliable, and less expensive than their pulsatile predecessors.