title: Separating in vivo mechanical stimuli for postpneumonectomy compensation: physiological assessment.
abstract: Following right pneumonectomy (PNX), the remaining lung expands and its perfusion doubles. Tissue and microvascular mechanical stresses are putative stimuli for initiating compensatory lung growth and remodeling, but their relative contributions to overall compensation remain uncertain. To temporally isolate the stimuli related to post-PNX lung expansion (parenchyma deformation) from those related to the sustained increase in perfusion (microvascular distention and shear), we replaced the right lung of adult dogs with a custom-shaped inflated prosthesis. Following stabilization of perfusion and wound healing 4 mo later, the prosthesis was either acutely deflated (DEF group) or kept inflated (INF group). Physiological studies were performed pre-PNX, 4 mo post-PNX (inflated prosthesis, INF1), and again 4 mo postdeflation (DEF) compared with controls with simultaneous INF prosthesis (INF2). Perfusion to the remaining lung increased ~76-113% post-PNX (INF1 and INF2) and did not change postdeflation. Post-PNX (INF prosthesis) end-expiratory lung volume (EELV) and lung and membrane diffusing capacities (DL(CO) and DM(CO)) at a given perfusion were 25-40% below pre-PNX baseline. In the INF group EELV, DL(CO) and DM(CO) remained stable or declined slightly with time. In contrast, all of these parameters increased significantly after deflation and were 157%, 26%, and 47%, respectively, above the corresponding control values (INF2). Following delayed deflation, lung expansion accounted for 44%-48% of total post-PNX compensatory increase in exercise DL(CO) and peak O(2) uptake; the remainder fraction is likely attributable to the increase in perfusion. Results suggest that expansion-related parenchyma mechanical stress and perfusion-related microvascular stress contribute in equal proportions to post-PNX alveolar growth and remodeling.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9034, USA.
authors.forename: D Merrill
authors.initials: DM
authors.lastname: Dane
authors.forename: Cuneyt
authors.initials: C
authors.lastname: Yilmaz
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Estrera
authors.forename: Connie C W
authors.initials: CC
authors.lastname: Hsia
mesh_terms: D056151:Airway Remodeling / Q000502:physiology*; D000818:Animals; D004285:Dogs; D008168:Lung / Q000098:blood supply / Q000502:physiology* / Q000601:surgery; D008176:Lung Volume Measurements / Q000379:methods; D008297:Male; D055806:Microvessels / Q000502:physiology*; D010477:Perfusion / Q000379:methods; D010805:Physical Conditioning, Animal / Q000502:physiology; D011013:Pneumonectomy / Q000379:methods; D019736:Prostheses and Implants; D011659:Pulmonary Gas Exchange / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D012129:Respiratory Function Tests / Q000379:methods; D013314:Stress, Mechanical; D014945:Wound Healing / Q000502:physiology*