Genetically altered mice provide a mechanism to define the in vivo phenotype of individual genes. This is especially relevant to genes implicated in producing myocardial diseases leading to congestive heart failure. The classic method to assess the hemodynamic phenotype in larger animals is through left ventricular (LV) pressure-volume (PV) analysis. However, determining absolute and instantaneous volume in the murine LV has been plagued by its small size and rapid heart rate. Conductance measurements offer an attractive solution to this problem by generating an instantaneous LV volume signal compatible with any myocardial size or heart rate. Unfortunately, the first generation conductance instrument generates an instantaneous conductance (volume) signal composed of blood and myocardium even at a single lower frequency. Only the blood component is desired for PV analysis. A mechanism to overcome this limitation is proposed by measuring admittance (complex conductance). Admittance is composed of both the magnitude of LV blood and myocardial conductance, and the phase angle of myocardial conductance. Traditional single frequency conductance measures only the magnitude of the conductance signal, which includes both the blood and myocardial components. Because measurable phase angle is unique to muscle, admittance offers a better method to determine and remove the instantaneous myocardial contribution to the combined LV conductance (volume) signal. The GOAL of this grant application is to develop, calibrate, and validate an INSTRUMENT to measure both the magnitude and the phase angle of the admittance signal in real time. To accomplish this goal, we will - 1) Develop both analog hardware and digital data acquisition Admittance Instruments, 2) Develop a more accurate method to derive LV volume from admittance measurements using FEM, and 3) Demonstrate that an Admittance Instrument is superior to traditional single frequency with MRI. ? ?
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