LV Volume Determinations: Mouse to Clinical Applications

描述（由申请人提供）：准确测定瞬时左心室（LV）容积是充血性心力衰竭药物和器械发现的重要工具。第一代电导仪器即使在单一低频下也能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液动力学表型的经典方法是通过LV压力-容量关系。由于小鼠心脏的尺寸小且心率快，确定LV的绝对和瞬时体积是不可能的。我们提出了一种机制来克服这种限制。复电导（导纳）测量LV血液和心肌电导的幅度以及心肌电导的相位角。我们建议，复电导提供了一个更好的方法来确定和消除瞬时心肌LV血容量测定的贡献。我们的目标是创建一个复杂的电导仪器，报告瞬时LV体积是准确和可靠的。该仪器将首次允许动物之间的比较以及患者之间的比较。我们的器械将在II期研究期间与传统电导仪器以及MRI（LV容量静态推导的金标准）进行比较。从长远来看，我们计划将我们的器械商业化到三个市场：1）作为小鼠遥测系统; 2）用于遥测和非遥测的大型动物，例如狗、猪、绵羊和灵长类动物; 3）供医生临床使用，以确定新药物和外科手术是否主要增加充血性心力衰竭患者的心肌收缩力或减少前负荷和后负荷。我们的具体目标是开发一种仪器和算法，从复电导（导纳）测量中获得瞬时LV体积。

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.