Permanent alveolar remodeling in canine lung induced by high-altitude residence during maturation

Abstract

Young canines born at sea level (SL) and raised for 5 mo at high altitude (HA, 3,800 m), followed by return to SL before somatic maturation, showed enhanced alveolar gas exchange and diffusing capacity at rest and exercise that persisted into adulthood (McDonough P, Dane DM, Hsia CC, Yilmaz C, Johnson RL Jr. J Appl Physiol 100: 474-81, 2006; Hsia CCW, Johnson RL Jr, McDonough P, Dane DM, Hurst MD, Fehmel JL, Wagner HE, Wagner PD. J Appl Physiol 102: 1448-55, 2007). To examine the associated structural response, we quantified lung ultrastructure in male foxhounds raised at 3,800 m HA or their littermates raised at SL (n = 6 each) from 2.5 to 7.5 mo of age. Three years following return to SL, lungs were fixed for morphometric analysis. In HA-exposed animals compared with SL controls, lung volume at a given inflation pressure was higher with enlargement of alveolar ducts and sacs without significant differences in the volumes of alveolar cell components, septal tissue, or in alveolar-capillary surface areas. There was a shift toward a significantly lower harmonic mean thickness of the blood-gas diffusion barrier in HA-raised animals. As a control organ, muscle capillary length density of costal diaphragm was significantly higher in HA-raised animals, indicating parallel adaptation in oxygen transport organs. We conclude that, in actively growing animals, 5 mo of HA exposure that was discontinued before somatic maturation induced acinar remodeling that increased lung compliance and reduced the resistance of blood-gas diffusion barrier to diffusion that persisted into adulthood, but without permanent enhancement of alveolar tissue growth.

Fig. 1.

Timeline of exposure. HA, high altitude; SL, sea level.

Fig. 2.

Representative lung sections from animals raised at SL (top) or HA (bottom) are shown stained with Masson's trichrome (left: blue for connective tissue, black for nuclei, and red/pink for cytoplasm) and Verhoff's elastic stain (right: black for elastic fibers and nuclei, red for collagen, and yellow for other tissue elements). Alveolar sacs (AS) have 0 to 1 opening; alveolar ducts (AD) are bounded by the tips of alveolar openings.

Fig. 3.

Frequency distribution of the harmonic thickness of blood-gas diffusion barrier measured as the length of test line intercepts from the epithelial surface to capillary erythrocyte membrane on electron micrographs. Data from the left lower lobe of 6 animals per group are classified in bins of different sizes. Values are means ± SD. *P ≤ 0.05 vs. SL control by ANOVA.