Ravikumar P, Yilmaz C, Bellotto DJ, Dane DM, Estrera AS, Hsia CC. Separating in vivo mechanical stimuli for postpneumonectomy compensation: imaging and ultrastructural assessment. J Appl Physiol 114: 961-970, 2013. First published January 17, 2013; doi:10.1152/japplphysiol.01394.2012.-Following right pneumonectomy (PNX), the remaining lung expands and its perfusion more than doubles. Tissue and microvascular mechanical stresses are putative stimuli for compensatory lung growth and remodeling, but their relative contribution remains uncertain. To temporally separate expansion- and perfusion-related stimuli, we replaced the right lung of adult dogs with a customized inflated prosthesis. Four months later, the prosthesis was either acutely deflated (DEF) or kept inflated (INF). Thoracic high-resolution computed tomography (HRCT) was performed pre- and post-PNX before and after prosthesis deflation. Lungs were fixed for morphometric analysis similar to 12 mo post-PNX. The INF prosthesis prevented mediastinal shift and lateral lung expansion while allowing the remaining lung to expand 27-38% via caudal elongation, associated with reversible capillary congestion in dependent regions at low inflation and 40-60% increases in the volumes of alveolar sepal cells, matrix, and fibers. Delayed prosthesis deflation led to further significant increases in lung volume, alveolar tissue volumes, and alveolar-capillary surface areas. At postmortem, alveolar tissue volumes were 33% higher in the DEF than the INF group. Lateral expansion explains similar to 65% of the total post-PNX increase in left lung volume assessed in vivo or ex vivo, similar to 36% of the increase in HRCT-derived (tissue + microvascular blood) volume, similar to 45% of the increase in ex vivo septal extravascular tissue volume, and 60% of the increase in gas exchange surface areas. This partition agrees with independent physiological measurements obtained in these animals. We conclude that in vivo signals related to lung expansion and perfusion contribute separately and nearly equally to post-PNX growth and remodeling.