Effect of severe calorie restriction on the lung in two strains of mice

There is a body of literature in animal models that has suggested the development of emphysema following severe calorie restriction. This has led to the notion of "nutritional emphysema" that might have relevance in COPD patients. There have been few studies, however, that have looked closely at both the mechanics and lung structure in the same animals. In the present work, we examined lung mechanics and histological changes in two strains of mice that have substantial differences in alveolar size, the C57BL/6 and C3H/HeJ strains. We quantified the dynamic elastance and resistance at 2.5 Hz, the quasistatic pressure volume curve, and the alveolar chord lengths in lungs inflated to a lung capacity at 25-30 cmH₂O. We found that after 2 or 3 wk of calorie restriction to 1/3 their normal diet, the lungs became stiffer with increased resistance. In addition, the lung capacity was also decreased. These mechanical changes were reversed after 2 wk on a normal ad libitum diet. Histology of the postmortem fixed lungs showed no changes in the mean alveolar chord lengths with calorie restriction. Although the baseline mechanics and alveolar size were quantitatively different in the two strains, both strains showed similar qualitative changes during the starvation and refeeding periods. Thus, in two strains of mice with genetically determined differences in alveolar size, neither the mechanics nor the histology show any evidence of emphysema-like changes with this severe caloric insult.