Dynamic Correction for Parallel Conductance , GP , and 1 Gain Factor , α , in Invasive Murine Left Ventricular 2 Volume Measurements

The conductance catheter technique could be improved by determining instantaneous parallel 40 conductance (GP) which is known to be time-varying, and by including a time-varying calibration factor in 41 Baan’s equation (α(t)). We have recently proposed solutions to the problems of both time-varying GP and time42 varying α, which we term “admittance” and “Wei’s equation”, respectively. We validate both our solutions in 43 mice, compared to the currently accepted methods, hypertonic saline (HS) to determine GP and Baan’s equation 44 calibrated with both stroke volume (SV) and cuvette. We performed simultaneous echocardiography in closed 45 chest mice (n=8) as a reference for left ventricular (LV) volume, and demonstrate that an off-center position for 46 the miniaturized Pressure-Volume (PV) catheter in the LV generates end-systolic and diastolic volumes 47 calculated by admittance with less error (p<0.03) (-2.49±15.33 μl error) compared to those same parameters 48 calculated by SV calibrated conductance (35.89±73.22 μl error), and by cuvette calibrated conductance 49 (-7.53±16.23 μl ES and -29.10±31.53 μl ED error). To utilize the admittance approach, myocardial permittivity 50 (εm) and conductivity (σm) were calculated in additional mice (n=7) and those results are used in this 51 calculation. In aortic banded mice (n=6) increased myocardial permittivity was measured (11844±2700 control, 52 21267±8005 banded, p<0.05), demonstrating that muscle properties vary with disease state. Volume error 53 calculated with respect to echo did not significantly change in aortic banded mice (6.74±13.06 μl, p=NS). 54 Increased inotropy in response to iv dobutamine was detected with greater sensitivity with the admittance 55 technique compared to traditional conductance (4.9±1.4 to 12.5±6.6 mmHg⋅μl Wei’s equation (p<0.05), 56 3.3±1.2 to 8.8±5.1 mmHg⋅μl using Baan’s equation (p=NS). New theory and method for instantaneous GP 57 removal, as well as application of Wei’s equation, are presented and validated in vivo in mice. We conclude that 58 for closed-chest mice, admittance (dynamic GP) and Wei’s equation (dynamic α) provide more accurate 59 volumes than traditional conductance, are more sensitive to inotropic changes, eliminate the need for hypertonic 60 saline, and can be accurately extended to aortic banded mice. 61 62 by 10.0.33.5 on O cber 0, 2017 http://jaysiology.org/ D ow nladed fom Dynamic GP and α Correction 3