Normally, exercise is limited by cardiovascular, not ventilatory factors. Theoretical calculations suggest that more than 50% of lung tissue may be resected before exercise performance becomes significantly limited. This is true in dogs where exercise capacity is relatively preserved after removal of the left lung. However, in human subjects after pneumonectomy, exercise capacity is impaired almost proportional to the amount of lung removed. Significant abnormalities in ventilatory mechanics, gas exchange and cardiovascular response develop during exercise. Comparisons between man and dog after pneumonectomy suggest several factors that might account for the exercise limitation in patients: 1 Gas exchange abnormalities, including ventilation-perfusion inhomogeneity and diffusion limitation. 2) Abnormal respiratory muscle mechanics, resulting in increased work of breathing and competition by the respiratory muscles for available 02 delivery. 3 ) Cardiovascular deconditioning; the patient is typically sedentary after pneumonectomy, whereas the dog is kept exercise trained. The objectives of this study are to define the sources and extents of exercise limitation due to gas exchange abnormalities (years 1 to 2), and to determine the potential benefit of cardiovascular fitness training on cardiovascular function, gas exchange and respiratory muscle energetics in patients after pneumonectomy (years 3 to 5). Ventilatory parameters, 02 consumption and pressure-volume work of breathing are measured continuously during progressive intensities of steady state ergometer exercise. Cardiac output, lung diffusing capacity, membrane diffusing capacity and pulmonary capillary blood volume will be measured by the rebreathing technique. The distribution of ventilation-perfusion ratios will be assessed by the multiple inert gas elimination technique. Pulmonary and systemic hemodynamics will be measured by catheterization. Energy requirement of the respiratory muscles will be measured by the resting isocapneic hyperventilation technique. The subjects will undergo an intensive 8-week ergometer training program. All measurements are repeated after training. Results from this study have broad long-term physiological and clinical applications, and may also be applicable to patients with other types of restrictive lung disease.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Lung Biology and Pathology Study Section (LBPA)
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University of Texas Sw Medical Center Dallas
Schools of Medicine
United States
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Hijazi, O M; Ramanathan, M; Estrera, A S et al. (1998) Fixed maximal stroke index in patients after pneumonectomy. Am J Respir Crit Care Med 157:1623-9
Hsia, C C; Chuong, C J; Johnson Jr, R L (1997) Red cell distortion and conceptual basis of diffusing capacity estimates: finite element analysis. J Appl Physiol 83:1397-404
Barazanji, K W; Ramanathan, M; Johnson Jr, R L et al. (1996) A modified rebreathing technique using an infrared gas analyzer. J Appl Physiol 80:1258-62
Wu, E Y; Ramanathan, M; Hsia, C C (1996) Role of hematocrit in the recruitment of pulmonary diffusing capacity: comparison of human and dog. J Appl Physiol 80:1014-20
Hsia, C C; Herazo, L F; Ramanathan, M et al. (1995) Cardiac output during exercise measured by acetylene rebreathing, thermodilution, and Fick techniques. J Appl Physiol 78:1612-6
Hsia, C C; Chuong, C J; Johnson Jr, R L (1995) Critique of conceptual basis of diffusing capacity estimates: a finite element analysis. J Appl Physiol 79:1039-47
Hsia, C C; McBrayer, D G; Ramanathan, M (1995) Reference values of pulmonary diffusing capacity during exercise by a rebreathing technique. Am J Respir Crit Care Med 152:658-65