Compensatory Lung Growth After Pneumonectomy

Pneumonectomy, the surgical removal of a lung, elicits a number of anatomical changes within the thoracic cavity that augments the diffusion capacity of the remaining lung. Pneumonectomy directs the entire cardiac output into the remaining lung and creates an empty hemithorax that results in a shift of the mediastinum toward the vacated thoracic compartment. In a number of experimental animal models, pneumonectomy initiates compensatory, regenerative growth of the remaining lung tissue that restores normal mass, structure and function. This growth process, called compensatory lung growth (CLG), is qualitatively similar across species, but differs with gender, age and hormonal status. CLG involves unique structure-function interactions not seen in solid organs. Little is known about the regenerative potential of human lungs. Although CLG has been reported in children after major lung resection, CLG in adults rarely occurs and remains a significant challenge. Mechanical feedback between the lung and thorax constitutes a major signal that sustains both post-natal lung development as well as post-pneumonectomy CLG. After pneumonectomy, increased mechanical stress and strain on the remaining lung induce adaptive responses to augment oxygen transport, including 1) recruitment of alveolarcapillary reserves, 2) remodeling of existing tissue, and 3) regenerative growth of acinar tissue when strain exceeds a critical threshold. This chapter will discuss the clinical aspects of pneumonectomy and will primarily review cellular and molecular mechanisms of CLG via experimental pneumonectomy models, which offers powerful insights into regenerative organ growth.