Conductance to Measure Cardiac Mechanics

DESCRIPTION (Applicant's Description Verbatim): The application of left ventricular pressure-volume relationships to transgenic mice to precisely measure contractility is not widely available. The long-term goal of this grant is to quantify left ventricular function in the intact mouse. Measurement of electrical conductance offers a method to generate an instantaneous left ventricular volume signal. The presently available instantaneous conductance output is a combination of blood and left ventricular muscle signals, but the blood volume (only) is desired. The problem can be solved by using two simultaneous frequencies, since myocardial resistivity varies with frequency while blood resistivity does not. The work will demonstrate that the dual frequency conductance system is superior to the standard single frequency system. A combination of experimental studies and numerical models will be used to calibrate the blood volume calculation when extracted from the combined blood and muscle signal. Finally, advances in instrumentation are proposed to move the dual frequency system to a closed-chest mouse preparation to enhance commercial interest. By removing the instantaneous myocardial contribution to the volume signal obtained during transient occlusion of the inferior vena cava, absolute measures of left ventricular contractility would be available. This would broaden the hemodynamic profile available from the intact murine left ventricle due to the wealth of information provided by pressure-volume analysis. PROPOSED COMMERCIAL APPLICATION: A dual frequency conductance system would allow scientists to precisely measure the complex phenotype of transgenic murine models of cardiovascular disease, such as congestive failure. Quantitation of left ventricular function would also allow the pharmaceutical industry to perform rapid screenting of new durgs in transgenic mice. The timing for these studies to understand the phenotype of selected genotypes is ideal as the Human Genome Project nears completion; and since humans and mice share a subset of highly conserved genes related to cardiovascular function.