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

项目摘要 一个简单、安全、可靠的机械替代品来替代衰竭的人类心脏将极大地影响健康 在乎在过去的四十年里，已经花费了大量的努力来开发心脏替代物， 设备（CRD），但技术障碍一直令人望而却步。恒流（CF）旋转泵介绍 在过去的7年中，血液泵已经彻底改变了心脏支持领域。这些泵更小 更节能，生产成本更低，比他们的脉动前辈，他们没有瓣膜 并且柔性膜使它们不受机械磨损的影响。已有1,000多名患者 使用CF泵治疗;首批植入的此类泵之一在6年多后功能良好。的 BRP项目的目标是证明下一代CRD包括两个集成的CF （HeartMate III）旋转泵可以提供充足的肺循环和体循环，以满足生理需求。 要求。本项目的具体目标是：（1）完善和改进全心脏置换术的CRD 使用结合工程和体内实验，使该设备允许小牛茁壮成长长达3 植入后3个月，并在恒定流中使用CRD比较小牛的生理学 （无脉）模式或被驱动以40次脉冲/分钟给予生理脉压;（2）观察 在肺和其他器官的微血管水平上无脉和减脉灌注的影响;以及 (3)评价CRD植入小牛的运动能力和CRD对以下因素的反应能力： 运动时代谢需求增加。这项研究应提供必要的证据， 从容积置换到CF技术的CRD发展的全球努力，将加速这一天的到来， “终末期心力衰竭的管理”可以从未满足的临床需求清单中划掉。的装配 该领域的先驱、创新人才、经验丰富的机构以及为这项工作提供的资源--以及 作为参与机构之间的长期合作， 临床试验-使该BRP团队能够成功实现其既定目标。

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.