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、可靠的机械替代衰竭的人类心脏将极大地影响医疗保健。在过去的四十年里，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，恒定流量（CF）旋转血泵的引入彻底改变了心脏支持领域。与脉动泵相比，这种泵体积更小，更节能，生产成本更低，而且没有阀门和柔性膜，因此不受机械磨损的影响。超过1000名患者接受了CF泵治疗；第一批植入的此类泵之一在6年多后功能良好。拟议的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。该项目的具体目标是：(1)通过结合工程和体内实验来完善和改进用于全心脏置换术的CRD，使该装置在植入后可以使小牛茁壮成长长达3个月，并比较在恒流（无脉）模式下使用CRD或驱动以给予40脉冲/分钟的生理脉压的小牛的生理状况；(2)观察肺等脏器微血管水平无脉和减脉灌注的效果；(3)评估植入CRD的犊牛的运动能力以及CRD在运动过程中应对代谢需求增加的能力。这项研究应该提供必要的证据，将全球在CRD开发方面的努力从容积置换技术转向CF技术，并将加速“终末期心力衰竭管理”从未满足的临床需求列表中划掉的那一天。该领域的先驱者、创新人才、经验丰富的机构和为这项工作提供的资源，以及参与机构之间的长期合作，最终实现了开创性的临床试验，这些都使BRP团队成功实现了既定目标。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、可靠的机械替代人类衰竭的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永久性心脏替代装置（CRD），它使用两个恒定流量的血液泵，比它们的脉动式前身更小，更高效，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.