Champion swimmers have significantly higher lung volumes and Dlco at a given exercise intensity than average subjects of comparable age, attributed to a higher Vc47–; differences may be partly due to genetic selection. Increasing ventilation and metabolic oxygen demand in animals via chronic cold exposure48or induced hyperthyroidism49have not led to enhanced lung growth or morphometric Dl estimated from structural parameters at postmortem. Dl correlates with enhanced lung growth in two models: high-altitude exposure and pneumonectomy. Natives born and raised at high altitude have higher lung volumes,50 Dlco, Dmco, and Vc than natives raised at sea level51; differences persist even after reacclimatization to sea level.52Immature dogs raised to maturity at high altitude show higher alveolar surface area, lung volume, and resting Dlco than control animals simultaneously raised at sea level.53 In immature dogs undergoing 55% lung resection by right pneumonectomy, vigorous compensatory lung growth returns resting Dlco to normal within 8 weeks.54 After reaching maturity, Dlco up to peak exercise is completely normal (Fig 4
, right), associated with normalization of septal cell volume and alveolar-capillary surface areas.,6 In adult dogs, there is no compensatory lung growth after 45% lung resection by left pneumonectomy55–; rather, recruitment of Dlco reserves in the remaining lung is the major source of functional compensation (Fig 4, left). Recruitment increases Dlco per lung unit by nearly 50%, mitigating the expected decline in Sao2, and maintaining a near-normal exercise capacity.56 In adult dogs after 55% lung resection by right pneumonectomy, physiologic reserves alone could not maintain adequate gas exchange during exercise, and limited compensatory septal tissue growth is also stimulated,57associated with a progressive increase in Dl with respect to Q̇.58 Physiologic Dl measured at peak exercise correlate highly with Dl estimated from structural parameters in the remaining lung postmortem.,6 In addition, perturbation in exercise Sao2 due to postpneumonectomy diffusion limitation could be accurately tracked from changes in Dl.,59 Thus, the DlQ̇ relationship can be used to noninvasively assess septal tissue growth.