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Sarcomeres Are Added in Series to Emphysematous Rat Diaphragm After Lung Volume Reduction Surgery^*

^* From the Department of Surgery (Drs. Shrager, Kim, Hashmi, Stedman, Zhu, and Kaiser) and the Pennsylvania Muscle Institute (Dr. Levine), the University of Pennsylvania School of Medicine, Philadelphia, PA.

Correspondence to: Joseph B. Shrager, MD, FCCP, CT Surgery, 6 Silverstein, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104; e-mail: jshrag{at}mail.med.upenn.edu

Study objectives: The diaphragm adapts to its shortened state in experimental emphysema primarily by losing sarcomeres in series, thus reducing its optimal operating length. One would expect improved diaphragmatic function after lung volume reduction surgery (LVRS) only if the muscle can readapt to its elevated, lengthened postoperative position by either adding back sarcomeres or lengthening sarcomeres. We used a model of elastase-induced emphysema in rats to test the hypothesis that sarcomere addition occurs following LVRS.

Design: A cohort of emphysematous rats was created by the intratracheal instillation of elastase. Five months after the instillation, one group of rats underwent measurement of in situ costal diaphragm length via laparotomy, the determination of optimal muscle fiber operating length (Lo) on stimulated diaphragm strips in vitro, and the measurement of sarcomere length by electron microscopy on strips fixed at Lo. Another group of rats underwent LVRS or sham sternotomy 5 months after the instillation, and 5 months following the operation these animals underwent the same series of diaphragmatic studies.

Results: Lo was significantly greater in rats that underwent LVRS than those that underwent sternotomy (mean [± SE] Lo after LVRS, 2.50 ± 0.08 cm; mean Lo after sternotomy, 2.27 ± 0.06 cm; p = 0.013). There was no significant difference in sarcomere lengths between the two groups (2.95 ± 0.04 vs 3.04 ± 0.04 µm, respectively; p = 0.10). Using Lo as the length basis, the mean sarcomere number was calculated to be 8,712 ± 192 in animals that had undergone LVRS and 7,144 ± 249 in animals that had undergone sternotomy (p < 0.001).

Conclusion: Sarcomere length is not significantly altered but sarcomeres are added in series following LVRS in this experimental model of emphysema/LVRS. It is likely that this sarcomere addition is a prerequisite to the improvement in inspiratory muscle function that has been observed following LVRS in humans.

Key Words: diaphragm • emphysema • respiratory muscles • sarcomeres

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