Dynamic correction for parallel conductance, GP, and gain factor, α, in invasive murine left ventricular volume measurements

Abstract

The conductance catheter technique could be improved by determining instantaneous parallel conductance (G(P)), which is known to be time varying, and by including a time-varying calibration factor in Baan's equation [alpha(t)]. We have recently proposed solutions to the problems of both time-varying G(P) and time-varying alpha, which we term "admittance" and "Wei's equation," respectively. We validate both our solutions in mice, compared with the currently accepted methods of hypertonic saline (HS) to determine G(P) and Baan's equation calibrated with both stroke volume (SV) and cuvette. We performed simultaneous echocardiography in closed-chest mice (n = 8) as a reference for left ventricular (LV) volume and demonstrate that an off-center position for the miniaturized pressure-volume (PV) catheter in the LV generates end-systolic and diastolic volumes calculated by admittance with less error (P < 0.03) (-2.49 +/- 15.33 microl error) compared with those same parameters calculated by SV calibrated conductance (35.89 +/- 73.22 microl error) and by cuvette calibrated conductance (-7.53 +/- 16.23 microl ES and -29.10 +/- 31.53 microl ED error). To utilize the admittance approach, myocardial permittivity (epsilon(m)) and conductivity (sigma(m)) were calculated in additional mice (n = 7), and those results are used in this calculation. In aortic banded mice (n = 6), increased myocardial permittivity was measured (11,844 +/- 2,700 control, 21,267 +/- 8,005 banded, P < 0.05), demonstrating that muscle properties vary with disease state. Volume error calculated with respect to echo did not significantly change in aortic banded mice (6.74 +/- 13.06 microl, P = not significant). Increased inotropy in response to intravenous dobutamine was detected with greater sensitivity with the admittance technique compared with traditional conductance [4.9 +/- 1.4 to 12.5 +/- 6.6 mmHg/microl Wei's equation (P < 0.05), 3.3 +/- 1.2 to 8.8 +/- 5.1 mmHg/microl using Baan's equation (P = not significant)]. New theory and method for instantaneous G(P) removal, as well as application of Wei's equation, are presented and validated in vivo in mice. We conclude that, for closed-chest mice, admittance (dynamic G(P)) and Wei's equation (dynamic alpha) provide more accurate volumes than traditional conductance, are more sensitive to inotropic changes, eliminate the need for hypertonic saline, and can be accurately extended to aortic banded mice.