Time course of and stimuli to compensatory growth of the lung after pneumonectomy.

Abstract

A B S T R A C T Left pneumonectomy in the mature rat led to an increase of [3H]thymidine incorporation into DNA of the remaining lung in the first 3 postoperative days, and resulted in a subsequent 38% increase of lung weight and 41% increase of lung tissue volume measured 1 wk after surgery. Despite these early changes, total lung volume (TLV) did not increase until the 2nd postoperative wk, reaching values 33% greater than in controls. Analysis of lung pressure-volume curves revealed that lung recoil was increased at low lung volumes 1 wk after surgery, but returned to normal by the 2nd postoperative wk, suggesting that synthesis of both lung elastin and collagen had occurred by this time. Increased inspired oxygen concentration (28% or 35%) during the 1st but not the 2nd postoperative wk abolished the change in TLV without influencing the increase in lung weight, while diminished inspired oxygen (17% or 14%) accentuated the postoperative increase in TLV. Lung pressure-volume curves demonstrated changes in distensibility at low lung volumes, suggesting that oxygen may have influenced synthesis or cross-linking of lung elastin. Alterations of minute ventilation in the postoperative period produced by 3% C02 did not influence the compensatory growth process, nor did administration of cyclophosphamide. These studies suggest that postpneumonectomy lung growth is a twophase process, beginning with cell proliferation and increased tissue volume, followed by increasing lung volume associated with formation of lung structural proteins. The latter process is profoundly influenced by inspired oxygen concentration in the early postoperative period.

Lung Growth and Airway Function after Lobectomy in Infancy for Congenital Lobar Emphysema

“…The consistent failure of the operated side to empty as completely as the other side by radiospirometry is evidence that recoil was lower on the side involved in volume compensation. Decreased recoil could reflect an abnormal elastin network (48) or abnormally large airspaces on the operated side (if volume compensation involved airspace enlargement). Early airway closure on the operated side could also explain these observations, but closing volumes were normal.…”

Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice

“…It was also documented by Brody (1) and Cagle and Thurlbeck (3) that the protein-to-DNA ratio was essentially constant over the postoperative time, indicating that the lung mass had been restored by hyperplastic growth (increase in cell number) rather than hypertrophic growth (increase in cell size). Despite these and other studies, the molecular mechanisms that trigger and regulate compensatory lung growth remain unknown.…”

“…Brody (1) reported from studies in rats and mice that the process of compensatory lung growth is completed 14 days postpneumonectomy when there is an early phase of cell proliferation within the first several days after surgery, followed by an increase in functional capacities. It was also documented by Brody (1) and Cagle and Thurlbeck (3) that the protein-to-DNA ratio was essentially constant over the postoperative time, indicating that the lung mass had been restored by hyperplastic growth (increase in cell number) rather than hypertrophic growth (increase in cell size).…”

Compensatory Lung Growth After Pneumonectomy

“…It is clear that CLG is very complex with multiple metabolic factors. Hyperinflation and stretch applied to the remaining lung after pneumonectomy are powerful signals to initiate CLG, and it is known that stretch of alveolar cells induces important changes associated with cell growth and septal formation, including signal transduction, protein turnover, growth factor production, proliferation, and apoptosis (Brody, 1975;Davies, et al, 1982;Fehrenbach, et al, 2008;Karl, et al, 1989). It appears that lung stress and strain generated after pneumonectomy, overlaid on a background of heightened developmental lung strain generated by the expanding thorax, intensifies the CLG responses.…”