LV Volume Determinations: Mouse to Clinical Applications

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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.