LV Volume Determinations: Mouse to Clinical Applications

左心室容量测定：小鼠临床应用

• 批准号: 6989659
• 负责人: Judith K Gwathmey
• 金额: $ 28.66万
• 依托单位: GWATHMEY, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6989659
• 关键词: bioengineering /biomedical engineering; biomedical equipment development; clinical biomedical equipment; computer program /software; computer system design /evaluation; heart conduction system; heart dimension /size; heart electrical activity; heart ventricle; intracardiac volume; laboratory mouse; myocardium

DESCRIPTION (provided by applicant): Determination of accurate instantaneous left ventricle (LV) volume is an important tool in drug and device discovery for congestive heart failure. First generation conductance instruments generate as instantaneous conductance (volume) signal composed of blood and myocardium even at a single low frequency. However, only the blood component is desired. Classic methods used to assess the hemodynamic phenotype in mammals are through LV pressure - volume relations. Due to the small size of the mouse heart and fast heart rate determining absolute and instantaneous volume of the LV has not been possible. We propose a mechanism to overcome this limitation. Complex Conductance (Admittance) measures both the magnitude of LV blood and myocardial conductance, as well as the phase angle of myocardial conductance. We propose that Complex Conductance offers a better method to determine and remove the instantaneous myocardial contribution to LV blood volume determinations. Our GOALS are to create a Complex Conductance Instrument that reports instantaneous LV volume that is accurate and reliable. The instrument will allow for the first time between animal comparisons as well as between patient comparisons. Our device will be compared during Phase 2 studies with traditional conductance instruments as well as MRI, the gold standard for static derivation of LV volume. Long term we plan to commercialize our devices to three markets 1) as a telemetered system in mice; 2) for use in larger animals both telemetered and non-telemetered e.g. dog, pig, sheep, and primates; and 3) for clinical use by physicians to determine whether new medications and surgical procedures are primarily increasing myocardial contractility or reducing preload and afterload in patients with congestive heart failure. Our SPECIFIC AIM is to develop an instrument and algorithms to derive instantaneous LV volume from Complex Conductance (Admittance) measurements.

描述（由申请人提供）：准确测定瞬时左心室（LV）容量是充血性心力衰竭药物和设备发现的重要工具。第一代电导仪器即使在单一低频下也会生成由血液和心肌组成的瞬时电导（体积）信号。然而，仅需要血液成分。用于评估哺乳动物血流动力学表型的经典方法是通过左心室压力-容量关系。由于小鼠心脏尺寸小且心率快，无法确定 LV 的绝对体积和瞬时体积。我们提出了一种机制来克服这一限制。复电导（导纳）测量左室血液和心肌电导的幅度，以及心肌电导的相位角。我们建议复数电导提供了一种更好的方法来确定和消除瞬时心肌对左心室血容量测定的贡献。我们的目标是创建一款复杂电导仪器，能够准确可靠地报告瞬时左心室容积。该仪器将首次允许在动物之间以及患者之间进行比较。我们的设备将在第二阶段研究期间与传统电导仪器以及 MRI（左室容量静态推导的黄金标准）进行比较。从长远来看，我们计划将我们的设备商业化到三个市场：1）作为小鼠遥测系统； 2) 用于大型动物，包括遥测和非遥测，例如：狗、猪、羊和灵长类动物； 3）供医生临床使用，以确定新药物和外科手术是否主要是增加心肌收缩力或减少充血性心力衰竭患者的前负荷和后负荷。我们的具体目标是开发一种仪器和算法，从复电导（导纳）测量中得出瞬时左心室容积。