Perfusion-related stimuli for compensatory lung growth following pneumonectomy

Abstract

Following pneumonectomy (PNX), two separate mechanical forces act on the remaining lung: parenchymal stress caused by lung expansion, and microvascular distension and shear caused by increased perfusion. We previously showed that parenchymal stress and strain explain approximately one-half of overall compensation; the remainder was presumptively attributed to perfusion-related factors. In this study, we directly tested the hypothesis that perturbation of regional pulmonary perfusion modulates post-PNX lung growth. Adult canines underwent banding of the pulmonary artery (PAB) to the left caudal (LCa) lobe, which caused a reduction in basal perfusion to LCa lobe without preventing the subsequent increase in its perfusion following right PNX while simultaneously exaggerating the post-PNX increase in perfusion to the unbanded lobes, thereby creating differential perfusion changes between banded and unbanded lobes. Control animals underwent sham pulmonary artery banding followed by right PNX. Pulmonary function, regional pulmonary perfusion, and high-resolution computed tomography of the chest were analyzed pre-PNX and 3-mo post-PNX. Terminally, the remaining lobes were fixed for detailed morphometric analysis. Results were compared with corresponding lobes in two control (Sham banding and normal unoperated) groups. PAB impaired the indices of post-PNX extravascular alveolar tissue growth by up to 50% in all remaining lobes. PAB enhanced the expected post-PNX increase in alveolar capillary formation, measured by the prevalence of double-capillary profiles, in both unbanded and banded lobes. We conclude that perfusion distribution provides major stimuli for post-PNX compensatory lung growth independent of the stimuli provided by lung expansion and parenchymal stress and strain.

Keywords: alveolar angiogenesis; lung resection; lung structure and function; pulmonary artery banding; pulmonary blood flow.

Fig. 1.

Flowchart of the experiments. HRCT, high-resolution CT; PNX, pneumonectomy.

Fig. 2.

Lung function measured under anesthesia pre- and post-PNX in PA-banding (PAB) and Sham-banding groups. A: static transpulmonary pressure-lung volume relationship. B: whole lung compliance. C: specific lung compliance (Cs) between 10- and 30-cmH₂O transpulmonary pressure. Means ± SD. P < 0.05 by repeated measures ANOVA: †PAB vs. Sham-banding groups; ‡post- vs. pre-PNX. NS, not significantly different (P > 0.05).

Fig. 3.

Pulmonary hemodynamics measured while standing at rest pre- and post-PNX in PA banding (PAB) and Sham-banding groups. A: cardiac output was measured by a thermodilution technique. B: mean pulmonary arterial (PA) pressure. C: pulmonary vascular resistance (PVR). Means ± SD. P < 0.05: *PAB vs. the corresponding Sham by factorial ANOVA; ‡post- vs. pre-PNX by repeated measures ANOVA.

Fig. 4.

Lobar blood flow measured by a microsphere technique while standing at rest. A and B: pre-PNX blood flow to the right (A) and left (B) lung lobes expressed as fractions of total blood flow. C: post-PNX blood flow to the remaining lobes, expressed as fractions of total blood flow. D: fold change (post-PNX/pre-PNX ratio) in lobar blood flow. Means ± SD. P ≤ 0.05: *PAB vs. corresponding Sham lobe by factorial ANOVA; †PAB vs. Sham across all lobes by repeated measures ANOVA; a, vs. left (L) cranial lobe; b, vs. left middle lobe; c, vs. right (R) cranial lobe; d, vs. right middle lobe; e, vs. right caudal lobe.

Fig. 5.

Representative HRCT images (panels at top) and FTV color maps (panels at bottom) of one animal pre-PNX and post-PNX in PA-banding and Sham-banding groups.

Fig. 6.

Fold changes (post-PNX/pre-PNX ratio) in HRCT-derived parameters in the left lung lobes of PAB and Sham-banding groups: air volume (A), tissue volume (B), and FTV (C). Means ± SD. P < 0.05: *PAB vs. corresponding Sham lobe; a, vs. corresponding left cranial lobe; b, vs. corresponding left middle lobe, by factorial ANOVA and Fisher's PLSD; †PAB vs. Sham across all lobes by repeated measures ANOVA.

Fig. 7.

Representative micrographs of post-PNX distal lung morphology in each lobe of the remaining left lung in PA-banding (PAB) and Sham-banding groups, compared with normal morphology in a separate cohort of unoperated adult animals (34). Stained with toluidine blue.

Fig. 8.

Morphometric results in the post-PNX remaining lobes of PAB and Sham-banding groups, shown as ratio with respect to the corresponding normal lobe in unoperated control animals (post-PNX/normal; A) (34), and ratio of PAB with respect to Sham banding (PAB/Sham; B). AT1 and AT2, alveolar type 1 and type 2 epithelium. Means ± SD. P < 0.05: *vs. 1.0 (the average in normal or Sham); †vs. the corresponding Sham. Factorial ANOVA.

Fig. 9.

Extravascular alveolar septal tissue volume (ml/kg; A) and prevalence of double-capillary profiles (percent of total [single + double] capillary profiles; B), in post-PNX remaining lobes of the left lung in PAB and Sham-banding groups, compared with the corresponding lobes of unoperated normal adult animals (34). Means ± SD. P < 0.05: *PAB vs. Sham; §vs. unoperated normal lobe. Factorial ANOVA. Examples of single- and double-capillary morphology are shown at right.