Quantifying in vivo stimuli for post‐pneumonectomy (PNX) alveolar growth: Contributions from increased perfusion and delayed lung expansion

Following right PNX, the remaining lung expands and its perfusion doubles. Tissue strain and microvascular shear are major stimuli for cellular growth but their contributions remain uncertain because earlier studies did not isolate the effects of perfusion. To temporally isolate expansion and perfusion ‐related stimuli, we replaced the right lung of adult foxhounds with an inflated prosthesis for 4 mo that was then either deflated (DEF, n=6) or kept inflated (INF, n=3) for 4 mo before lung fixation and morphometry. Results were compared to the normal L lung.Volume (ml.kg −1 ) INF DEFFixed lung 35.86±6.09 * 47.08±8.07 * † Alveolar tissue 1.45±0.40 * 1.93±0.28 * † Epithelium 0.59±0.15 * 0.73±0.15 * Interstitium 0.53±0.17 * 0.73±0.08 * † Endothelium 0.32±0.09 0.45±0.08 * † Capillary blood 2.07±0.53 * 2.39±0.37 *Mean±SD P≤0.05 by ANOVA: * vs control, † vs INF.Perfusion increased post‐PNX and did not change following DEF. Lung and alveolar tissue volumes were 32% higher in the DEF group than INF group. Overall, 45% of the increase in the volumes of alveolar cell components and surface areas could be attributed to delayed lung expansion and the rest to an increase in perfusion and possibly other factors. This partition is consistent with estimates based on functional compensation, suggesting that in vivo tissue and microvascular mechanical stresses contribute equally to post‐PNX lung growth. Support: NHLBI R01‐HL40070, 62873