Pulmonary Vascular Resistance and Impedance in Isolated Mouse Lungs: Effects of Pulmonary Emboli

Abstract

To study pulsatile pressure-flow rate relationships in the intact pulmonary vascular network of mice, we developed a protocol for measuring pulmonary vascular resistance and impedance in isolated, ventilated, and perfused mouse lungs. We used pulmonary emboli to validate the effect of vascular obstruction on resistance and impedance. Main pulmonary artery and left atrial pressures and pulmonary vascular flow rate were measured under steady and pulsatile conditions in the lungs of C57BL/6J mice (n = 6) before and after two infusions with 25 μm-diameter microspheres (one million per infusion). After the first and second embolizations, pulmonary artery pressures increased approximately two-fold and three and a half-fold, respectively, compared to baseline, at a steady flow rate of 1 ml/min (P < 0.05). Pulmonary vascular resistance and 0 Hz impedance also increased after the first and second embolizations for all flow rates tested (P < 0.05). Frequency-dependent features of the pulmonary vascular impedance spectrum were suggestive of shifts in the major pulmonary vascular reflection sites with embolization. Our results demonstrate that pulmonary artery pressure, resistance, and impedance magnitude measured in this isolated lung setup changed in ways consistent with in vivo studies in larger animals and humans and demonstrate the usefulness of the isolated, ventilated, and perfused mouse lung for investigating steady and pulsatile pressure-flow rate relationships.