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J Appl Physiol 104: 1069-1079, 2008. First published February 7, 2008; doi:10.1152/japplphysiol.01198.2007
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Shifting sources of functional limitation following extensive (70%) lung resection

Connie C. W. Hsia,1 D. Merrill Dane,1 Aaron S. Estrera,2 Harrieth E. Wagner,3 Peter D. Wagner,3 and Robert L. Johnson, Jr.1

1Departments of Internal Medicine and 2Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas; and 3Department of Medicine, University of California, San Diego, La Jolla, California

Submitted 1 July 2007 ; accepted in final form 16 January 2008

We previously found that, following surgical resection of ~58% of lung units by right pneumonectomy (PNX) in adult canines, oxygen-diffusing capacity (DLO2) fell sufficiently to become a major factor limiting exercise capacity, although the decline was mitigated by recruitment, remodeling, and growth of the remaining lung units. To determine whether an upper limit of compensation is reached following the loss of even more lung units, we measured pulmonary gas exchange, hemodynamics, and ventilatory power requirements in adult canines during treadmill exercise following two-stage resection of ~70% of lung units in the presence or absence of mediastinal distortion. Results were compared with that in control animals following right PNX or thoracotomy without resection (Sham). Following 70% lung resection, peak O2 uptake was 45% below normal. Ventilation-perfusion mismatch developed, and pulmonary arterial pressure and ventilatory power requirements became markedly elevated. In contrast, the relationship of DLO2 to cardiac output remained normal, indicating preservation of DLO2-to-cardiac output ratio and alveolar-capillary recruitment up to peak exercise. The impairment in airway and vascular function exceeded the impairment in gas exchange and imposed the major limitation to exercise following 70% resection. Mediastinal distortion further reduced air and blood flow conductance, resulting in CO2 retention. Results suggest that adaptation of extra-acinar airways and blood vessels lagged behind that of acinar tissue. As more lung units were lost, functional compensation became limited by the disproportionately reduced convective conductance rather than by alveolar diffusion disequilibrium.

pneumonectomy; exercise; lung diffusing capacity; ventilation-perfusion distribution; pulmonary arterial hypertension; dysanaptic lung growth; work of breathing



Address for reprint requests and other correspondence: C. C. W. Hsia, Pulmonary and Critical Care Medicine, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9034




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C. Yilmaz, P. Ravikumar, D. M. Dane, D. J. Bellotto, R. L. Johnson Jr., and C. C. W. Hsia
Noninvasive quantification of heterogeneous lung growth following extensive lung resection by high-resolution computed tomography
J Appl Physiol, November 1, 2009; 107(5): 1569 - 1578.
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