A Non-Blood Contacting Muscle Powered VAD for Chronic Circulatory Support

 描述（由申请人提供）：短期使用左心室辅助装置（LVAD）已被证明可以逆转充血性心力衰竭的影响，充血性心力衰竭是一种毁灭性的疾病，最终将折磨每五个美国人中的一个。然而，当用于永久性支持时，LVAD治疗受到经皮传动线和血液接触表面引起的严重并发症的限制。在这里，我们建议组装和测试一个非血液接触肌肉动力LVAD系统，避免了目前的心脏辅助设备的限制，因此可能代表了充血性心力衰竭治疗的重大进展。作为实现这一目标的第一步，我们开发了一种可植入的肌肉能量转换器（MEC），能够将收缩能量转化为液压动力。本项目的目的是组装和测试由该器械驱动的非血液接触心室辅助系统。要测试的中心假设是，条件骨骼肌的机械功率可以通过MEC转换为液压能，并用于驱动永久性心脏辅助装置。所提出的研究背后的基本原理集中于以下事实：骨骼肌响应于慢性激活而表达氧化（抗疲劳）表型，并且训练的背阔肌（LD）肌肉已被证明以与长期心脏辅助相容的速率进行工作。因此，考虑到目前用于充血性心力衰竭的医学治疗的局限性、与输送体外动力以帮助衰竭的心脏相关的困难以及由血液接触表面引起的严重并发症，有必要进行开发和测试非血液接触的肌肉动力血泵的研究。为了实现本研究的目标，提出了以下三个具体目标：1）构建mVAD原型装置并在台架上进行测试，以记录功能参数并评估长期机械可靠性; 2）植入原型mVAD系统（急性实验）以改进植入方法，评价解剖学匹配，并记录组织/器械界面的急性生物反应;和3）在心力衰竭动物中进行短期（28天）植入研究，以建立体内系统功能，记录组织/器械界面处的慢性生物反应，量化血液动力学效应，并确定mVAD系统的总体功效。我们的期望是，在拟议的支持期结束时，我们将证明利用原位肌肉能量进行长期循环支持的可行性。我们进一步期望，该技术的实际应用将通过完整的肌肉驱动的心室辅助系统的体内评价得到证明。

 DESCRIPTION (provided by applicant): Short-term use of left ventricular assist devices (LVADs) has been shown to reverse the effects of congestive heart failure, a devastating condition that will ultimately afflict one in every five Americans. When used for permanent support however, LVAD therapy has been limited by serious complications caused by percutaneous drivelines and blood contacting surfaces. Here we propose to assemble and test a non-blood-contacting muscle-powered LVAD system that avoids the limitations of current heart assist devices and so could potentially represent a major advance in the treatment of congestive heart failure. As a first step toward this goal, we have developed an implantable muscle energy converter (MEC) capable of transforming contractile energy into hydraulic power. The objective of this project is to assemble and test a non-blood- contacting ventricular assist system powered by this device. The central hypothesis to be tested is that the mechanical power of conditioned skeletal muscle can be converted into hydraulic energy by the MEC and used to drive a permanent cardiac assist device. The rationale behind the proposed research centers on the fact that skeletal muscles express oxidative (fatigue-resistant) phenotypes in response to chronic activation and that trained latissimus dorsi (LD) muscles have been shown to perform work at rates compatible with long- term cardiac assistance. Thus, given the limitations of current medical therapies for congestive heart failure, the difficulties associated with delivering extracorporeal power to aid the failing heart, and the serious complications cause by blood contacting surfaces, research to develop and test a non-blood-contacting muscle-powered blood pump is warranted. To accomplish the objectives of this research, the following three specific aims are proposed: 1) Build mVAD prototype devices and test on the bench to document functional parameters and assess long- term mechanical reliability; 2) Implant prototype mVAD systems (acute experiments) to refine implantation methods, evaluate anatomic fit, and document acute biological reactions at the tissue/device interface; and 3) Perform short-term (28-day) implant studies in animals with heart failure to establish in vivo system functionality, document chronic biological reactions at the tissue/device interface, quantify hemodynamic effects, and determine the overall efficacy of the mVAD system. Our expectations are that, at the conclusion of the proposed period of support, we will have demonstrated the viability of harnessing energy from in situ muscle for long-term circulatory support. We further expect that practical application of this technology will have been demonstrated via in vivo evaluation of a complete muscle-actuated ventricular assist system.