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

项目总结 一种简单、安全、可靠的心脏衰竭机械替代物将极大地影响健康。 关心。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品。 设备(CRD)，但技术障碍令人望而却步。恒流(CF)旋转机简介 血泵在过去的7年里使心脏支持领域发生了革命性的变化。这些泵更小， 与脉动的前辈相比，它们的能效更高，生产成本更低，而且它们没有阀门 而柔软的薄膜使它们不受机械磨损的影响。已有1000多名患者接受了 经过CF泵处理；第一批植入的此类泵之一在6年多后仍可正常工作。这个 拟议的业务流程计划项目的目标是显示下一代CRD包括两个集成的CF (HeartMate III)旋转泵可以提供足够的肺循环和体循环，以满足生理需求 要求。该项目的具体目标是：(1)完善和完善全心脏置换的CRD 利用工程学和活体实验相结合的方法，该设备可以让小牛犊在长达3年的时间里茁壮成长 植入后3个月，比较CRD在恒流状态下的生理学变化 (无脉冲)模式或激励以40脉冲/分钟施加生理脉压；(2)观察 在肺和其他器官的微血管水平上无脉搏和减少脉搏灌流的影响；以及 (3)评价植入CRD的犊牛的运动能力和CRD的反应能力 运动过程中代谢需求增加。这项研究应该为转移提供必要的证据 全球在CRD方面的努力从批量置换发展到CF技术，并将加速 “终末期心力衰竭的治疗”可以从未得到满足的临床需求清单上划掉。聚集在一起的 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 作为参与机构之间的长期合作，最终导致了 临床试验-BRP团队成功实现其既定目标的独特定位。

PROJECT SUMMARY 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 to successfully achieve its stated goals.