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Laboratory and Animal Investigations |

Size and Composition Changes in Diaphragmatic Fibers in Rats Exposed to Chronic Hypercapnia*

Miho Kumagai, MD; Tetsuri Kondo, MD; Yasuyo Ohta, MD, FCCP; Tadayuki Ishihara, MD
Author and Funding Information

*From the Department of Medicine (Drs. Kumagai, Kondo, and Ohta), Tokai University School of Medicine, Isehara, Japan; and the Department of Medicine (Dr. Ishihara), National Higashi-Saitama Hospital, Hasuda, Japan.

Correspondence to: Tetsuri Kondo, MD, Department of Pulmonary Medicine, Tokai University School of Medicine, Isehara, 259–193 Japan; e-mail: tetsuri@is.icc.u-tokai.ac.jp



Chest. 2001;119(2):565-571. doi:10.1378/chest.119.2.565
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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 (V̇e) 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) Paco2 after 19 weeks of sustained hypercapnia was 71.0 ± 4.7 mm Hg. The V̇e 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.

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