Size and composition changes in diaphragmatic fibers in rats exposed to chronic hypercapnia

Objective: To test the hypothesis that chronic hypercapnia changes the composition of the respiratory muscle by continuous augmentation of ventilation. Materials and methods: Eighteen male Wistar rats were housed in 10% CO2 in air for 19 weeks, and their minute ventilation ((V) over dot E) was measured every 6 weeks. The diaphragm, excited at 19 weeks of exposure, was classified as fiber type I, IIa, or IIb. Cross-sectional areas of individual fibers were measured. Fibers with a target-like appearance on reduced nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR) stain also were counted, The data were compared with those of rats kept in room air. Results: The mean (+/- SD) Pace, after 19 weeks of sustained hypercapnia was 71.0 +/- 4.7 mm Hg. The (V) over dot E remained at a high level until 12 weeks of exposure, and then it significantly decreased at week 18. In a comparison with the control rats, a larger number of type I fibers and a smaller number of type IIb fibers were found in the diaphragm of the chronically hypercapnic rats. In addition, the latter group's cross-sectional area revealed fibers of a significantly smaller diameter. Target-like fibers were observed in 5% of the NADH-TR-stained fibers in the chronically hypercapnic rats but were not seen in the control rats. Conclusion: By increasing the ratio of fatigue-resistant fibers, the diaphragm was able to adapt to a sustained load induced by hypercapnia. However, this adaptive process was accompanied by a degenerative change in the tissue.