Defining a stimuli-response relationship in compensatory lung growth following major resection

Abstract

Major lung resection is a robust model that mimics the consequences of loss-of-functioning lung units. We previously observed in adult canines, following 42% and 58% lung resection, a critical threshold of stimuli intensity for the initiation of compensatory lung growth. To define the range and limits of this stimuli-response relationship, we performed morphometric analysis on the remaining lobes of adult dogs, 2-3 years after surgical removal of ∼ 70% of lung units in the presence or absence of mediastinal shift. Results were expressed as ratios to that in corresponding control lobes. Lobar expansion and extravascular tissue growth (∼ 3.8- and ∼ 2.0-fold of normal, respectively) were heterogeneous; the lobes remaining next to the diaphragm exhibited a greater response. Tissue growth and capillary formation, indexed by double-capillary profiles, increased, regardless of mediastinal shift. Septal collagen fibers increased up to 2.7-fold, suggesting a greater need for structural support. Compared with previous cohorts following less-extensive resection, tissue volume and gas-exchange surface areas increased significantly only in the infracardiac lobe following 42% resection, exceeded two- to threefold in all lobes following 58% resection, and then exhibited diminished gains following ∼ 70% resection. In contrast, alveolar-capillary formation increased with incremental resection without reaching an upper limit. Overall structural regrowth was most vigorous and uniform following 58% resection. The diminishment of gains in tissue growth, following ∼ 70% resection, could reflect excessive or maldistributed mechanical stress that threatens septal integrity. Results also suggest additional independent stimuli of alveolar-capillary formation, possibly related to the postresection augmentation of regional perfusion.