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.

METHODS

Eighteen male Wistar rats were housed in 10% CO(2) in air for 19 weeks, and their minute ventilation V(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) PaCO(2) after 19 weeks of sustained hypercapnia was 71.0 +/- 4.7 mm Hg. The V(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.

CONCLUSIONS

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.