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

描述(由申请人提供)：一种简单、安全、可靠的心脏衰竭机械替代物将极大地影响医疗保健。在过去的40年里，人们花费了大量的精力来开发心脏替代装置(CRD)，但技术障碍一直令人望而却步。在过去的7年里，恒流(CF)旋转式血泵的引入使心脏支持领域发生了革命性的变化。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。已有1,000多名患者接受了CF泵的治疗；6年多后，第一批植入这种泵的患者之一就开始工作了。拟议的BRP项目的目标是证明，由两个集成的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。该项目的具体目标是(1)利用工程学和体内实验相结合的方法，完善和改进用于全心脏置换的CRD，使该装置能够让犊牛在植入后长达3个月的时间内茁壮成长，并比较在恒流(无脉冲)模式下和在驱动下以40脉冲/分钟的生理脉压施加CRD的犊牛的生理状况；(2)从肺和其他器官的微血管水平观察无脉和减少脉冲灌流的影响；(3)评估植入CRD的犊牛的运动能力和CRD应对运动中增加的代谢需求的能力。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技术转移到CF技术，并将加速“终末期心力衰竭的管理”可以从未满足的临床需求清单中删除的那一天。该领域的先驱、创新人才、经验丰富的机构和为这项工作提出的资源--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团队处于独特的地位，能够成功地实现其既定目标。与公共健康相关：在美国，心力衰竭是导致过早死亡的主要原因。一种简单、安全、可靠的机械替换正在衰竭的人类心脏将对医疗保健产生巨大影响。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替代装置(CRD)，这两个泵比它们的脉动前身更小、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.