2007-08-24 10:40

S-5 Marc D. Feldman, M.D.

【演題名】
Advances in invasive murine cardiovascular studies
ネズミを用いた侵襲性の心血管研究における進歩

1Rodolfo J. Trevino, 4Douglas L. Jones, 3John Porterfield, 3Anil Kottam, 2Gary B. Chisholm, 1Daniel Escobedo, 1Amanda Barton, 3Jon Valvano, 3John Pearce, 1,3Marc D. Feldman

1- Department of Medicine, University of Texas Health Science Center in San Antonio, Texas;
2- Department of Epidemiology and Biostatistics, University of Texas Health Science Center in San Antonio, Texas;
3- Department of Electrical Engineering, School of Engineering, University of Texas at Austin, Texas; and
4- Departments of Physiology, Pharmacology and Medicine, University of Western Ontario, Canada.

There is interest in generating accurate invasive left ventricular (LV) pressure-volume (PV) relations in gene altered mice. The current systems are based upon the magnitude of the conductance signal (old fashion conductance). There are two limitations which limit this approach. First, the electric field is not homogenous and thus the conductance to volume relationship is non-linear. Second, there is leakage of current into the myocardium which contaminates the conductance signal, when only the blood signal is desired. We have developed a solution to the second problem. We propose the use of complex admittance as a new approach to generate LV PV relations with removal of instantaneous parallel conductance. The admittance approach takes advantage of myocardium having both real and imaginary components, whereas blood only has real components, which allows us to remove the myocardium from the combined blood-myocardial signal. Such an approach eliminates the use of hypertonic saline in the mouse, and can generate absolute ventricular function measures such as end-systolic elastance, allowing mouse-to-mouse comparisons for the first time. A comparison of magnitude only conductance at 2 kHz versus admittance at 30 kHz derived LV PV relations acquired at the same time in the same murine heart will be presented.

Due to the demanding design constraints created by the intact murine heart, developing a micro-manometer pressure sensor that has little temperature or pressure drift, a flat frequency response to at least ten times the murine heart rate, and adequate sensitivity has been difficult. Millar Instruments successfully solved this problem in 1998, and since that time, the 1.4 F Millar micro-manometer pressure sensor has served as the “gold standard” for invasive cardiovascular murine studies. Recently, Scisence Inc. has developed a competing micro-manometer pressure sensor for cardiovascular applications in the mouse. It was designed with the sensor being recessed inside the protective housing with a circumference of 1.2 F. However, despite use of this new Scisense pressure sensor by the cardiovascular research community, the Scisense sensor has not been previously tested in a rigorous fashion to validate its use in the murine heart. We demonstrate that both sensors had equivalent in vitro swept frequency response over time, frequency response at 100mmHg, and catheter step response to transient pressure drop. Both sensors also performed similarly during in vivo dose-response studies to iv isoproterenol, and simultaneous placement of both micro-manometer pressure sensors in the same intact murine heart. However, the Millar sensor had slightly greater in vitro temperature drift and in vivo pressure drift. We conclude that both sensors are equivalent, and that the Scisense pressure sensor represents an alternative to the Millar micro-manometer pressure sensor.