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

恒流全心脏置换装置引起的脉冲效应

• 批准号: 7735978
• 负责人: O. H. FRAZIER
• 金额: $ 82.64万
• 依托单位: TEXAS HEART INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7735978
• 关键词: Abbreviations; Adherens Junction; Affect; Animals; Attenuated; Belief; Biomedical Engineering; Blood Circulation; Bypass; Cardiac; Cardiopulmonary Bypass; Cardiovascular system; Cessation of life; Characteristics; Clinical; Clinical Trials; Collaborations; Development; Device or Instrument Development; Devices; Engineering; Equilibrium; Evolution; Exercise; Goals; Healthcare; Heart; Heart Research; Heart failure; Human; Implant; Induced Heart Arrest; Institution; Laboratories; Left; Left ventricular structure; Light; Lung; Mechanics; Membrane; Metabolic; Modeling; Moderate Exercise; New York; Organ; Output; Patients; Perfusion; Peripheral; Physiologic pulse; Physiological; Physiology; Plant Leaves; Positioning Attribute; Prosthesis; Pulmonary Circulation; Pulse Pressure; Pump; Quality of life; Recording of previous events; Research; Resources; Skeletal Muscle; Speed; Staging; System; Talents; Techniques; Technology; Testing; United States; Vascular resistance; Venous; Work; blood pump; clinical application; design; experience; flexibility; implantable device; implantation; improved; in vivo; innovation; meetings; methionylmethionine; next generation; premature; pressure; public health relevance; research study; response; time interval; total artificial heart; ventricular assist device

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.

描述（由申请人提供）：一种简单、安全、可靠的机械替代衰竭人类心脏的方法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），但技术障碍却令人望而却步。过去 7 年恒流 (CF) 旋转血泵的推出彻底改变了心脏支持领域。与之前的脉动泵相比，这些泵更小、更节能、生产成本更低，而且它们没有阀门和柔性膜，因此不受机械磨损的影响。超过1000名患者接受了CF泵的治疗；第一批植入的此类泵之一在六年多后运行良好。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 可以提供足够的肺和全身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全心脏置换的CRD，使该装置能够让小牛在植入后存活长达3个月，并比较不同心脏置换的生理学情况。小牛在恒流（无脉冲）模式下使用 CRD 或以 40 脉冲/分钟的速度施加生理脉冲压力； (2) 观察无脉冲和减脉冲灌注在肺和其他器官微血管水平上的效果； (3) 评估植入 CRD 的小牛的运动能力以及 CRD 对运动期间增加的代谢需求做出反应的能力。这项研究应该提供必要的证据，将全球 CRD 开发工作从容量置换转向 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清单中划掉的那一天。该领域的先驱者、创新人才、经验丰富的机构和为本项工作提出的资源，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 团队拥有独特的地位，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、可靠的机械替代品可以替代人类衰竭的心脏，这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），与之前的脉动式血泵相比，该装置更小、更高效、更可靠且更便宜。