Measurement of Pulmonary Impedance in Live Mice and Changes With Chronic Hypoxia

Pulmonary arterial impedance offers the most complete characterization of right ventricular afterload, which is crucial for the proper function of the right ventricle. Impedance can be calculated in either the time or frequency domain from pulsatile pressure-flow relationships. Here we compared impedance metrics calculated in the time domain to those computed in the frequency domain under normal conditions and after induction of hypoxic pulmonary hypertension (HPH) (10 and 21 days). In C57BL6/J mice, pulmonary arterial pressure was measured invasively with a high fidelity catheter while pulmonary arterial flow was measured with Doppler ultrasound. Input impedance (Z₀) and characteristic impedance (Z_C) were calculated from the resulting pressure-flow relationships. Our results demonstrate that Z₀ increased with 10 days of hypoxia as expected but surprisingly returned toward normal after 21 days; the values obtained were not different for the two methods (R² = 0.99, P <0.0001). Z_C increased slightly but not significantly with 10 days of hypoxia and remained at control levels after a 21 day exposure; here the values did depend on the method used: Z_C was 1.73 times larger when calculated in the frequency domain versus the time domain (R² = 0.86, P <0.0001). We conclude that both time and frequency domain analyses can be used to calculate important metrics of pulmonary vascular impedance, which lend insight into the changes in arterial structure and function that occur with pulmonary vascular disease.