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

Left pneumonectomy in the mature rat led to an increase of [3Ha1 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% CO2 did not influence the compensatory growth process, nor did administration of cyclophosphamide. These studies suggest that postpneumonectomy lung growth is a two-phase 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.