Mechanostructural adaptations preceding postpneumonectomy lung growth

Abstract

In many species, pneumonectomy results in compensatory growth in the remaining lung. Although the late mechanical consequences of murine pneumonectomy are known, little is known about the anatomic adaptations and respiratory mechanics during compensatory lung growth. To investigate the structural and mechanical changes during compensatory growth, mice were studied for 21 days after left pneumonectomy using microCT and respiratory system impedance (FlexiVent). Anatomic changes after left pneumonectomy included minimal mediastinal shift or chestwall remodeling, but significant displacement of the heart and cardiac lobe. Mean displacement of the cardiac lobe centroid was 5.2±0.8mm. Lung impedance measurements were used to investigate the associated changes in respiratory mechanics. Quasi-static pressure-volume loops demonstrated progressive increase in volumes with decreased distensibility. Measures of quasi-static compliance and elastance were increased at all time points post pneumonectomy (p < 0.01). Oscillatory mechanics demonstrated a significant change in tissue impedance on the 3rd day after pneumonectomy. The input impedance on day 3 after pneumonectomy demonstrated a significant increase in tissue damping (5.8 versus 4.3 cmH2O/ml) and elastance (36.7 versus 26.6 cmH2O/ml) when compared to controls. At all points, hysteresivity was unchanged (0.17). We conclude that the timing and duration of the mechanical changes was consistent with a mechanical signal for compensatory growth.

Effect of unilateral diaphragmatic paralysis on postpneumonectomy lung growth

“…In contrast to the three lobes in the human right lung, rodents have an additional posterior mediastinal lobe, variously referred to as the cardiac, retrocaval, or median lobe. Prior studies have demonstrated that the cardiac lobe is displaced in the left hemithorax after PNX (8,10). Intriguingly, the cardiac lobe demonstrates the greatest relative increase in compensatory lung growth (17).…”

“…Preliminary experiments in our laboratory demonstrated that the chest wall contributed less than 15% to absolute impedance measurements and did not influence the time course or reproducibility of the observed mechanical changes in the lung (8,10). The constant-phase model (11) was fit to the input impedance to derive Newtonian resistance (R n), tissue damping (G), tissue elastance (H), and hysteresivity () as described below:…”

“…Lung volumes were measured using the Flexivent (SciReq) rodent ventilator (8). The animals were hyperventilated at a rate of 300/min to remove spontaneous respiratory drive.…”

Structural and functional evidence for the scaffolding effect of alveolar blood vessels

“…Mice undergoing surgical resection had constant heart rate and oximetry monitoring [13]. In mice undergoing surgical resection, the anterior chestwall was removed and lobar exclusion performed by clamp occlusion of the lobar bronchus and corresponding arterial blood supply.…”

“…Prior to all measurements, the pressure transducers and ventilator tubing of the FlexiVent (SciReq, Montreal, QC) were calibrated as described [13]. After intubation, mice were transferred to the FlexiVent system (SciReq) for pulmonary mechanics studies.…”