Pulmonary Rehabilitation Improves Exercise Capacity And Molecular Skeletal Muscle Adaptation In Pulmonary Emphysema Patients

Purpose: Chronic pulmonary emphysema (PE) exerts a sustained reduction in arterial oxygen saturation associated with decreased exercise capacity, habitual movement and impaired structural composition of skeletal muscle. In particular, decreased mitochondrial- and capillary density but an increased expression of glycolytic fibers, serve as indicators for deteriorated skeletal muscle integrity and lack of oxidative capacity in these patients. Hypothesis: Because exercise is a major stimulus for the maintenance of skeletal muscle oxidative capacity, we hypothesized that regular exercise will adapt also skeletal muscle of PE patients towards increased capillary- and mitochondrial density and enhanced exercise capacity. Methods: 20 PE patients (Stage 4, 57 ±7 years, BMI 27 ±7, FeV1% 31 ± 7) were subjected to 3 weeks pulmonary rehabilitation (PR) including strength and endurance exercise under oxygen application. PRE and POST skeletal muscle biopsies from vastus lateralis were collected and immunohistochemistry and western blotting used to detect changes in molecular signaling and structural skeletal muscle adaptation. 6min walking distance (6MWT) and power output (PWR) were determined on a treadmill and cycling ergometer as markers for general exercise capacity. Results: From PRE to POST: 1. Significant increase in 6MWT and PWR during ergometry (P<0.01); 2. Significant increase in capillary to fiber ratio in type I (P<0.05) and type II fibers (p =0.16). 3. Significant reduction in the percentage of fast glycolytic IIA-IIX hybrid fibers (P<0.05). 4. Increased expression of mitochondrial signaling via TFAM (mitochondrial transcription factor A) and PGC-1α (P<0.01 and P<0.05). 5. Significant increase of cytochrome c-oxidase activity in type I (P<0.01) and type IIA fibers (P<0.05). 6. Significantly increased nuclear localization of transcription factors involved in oxidative fiber type expression (MEF2; NFATC2) (both P<0.01). Conclusion: A short term PR stimulates skeletal muscle adaptability and physical performance of stage 4 PE patients towards higher exercise capacity associated with beneficial skeletal muscle adaptation. The obligatory and repeated application of PR might help to sustain minimal exercise capacity reduce co-morbidity and improve quality of life in these patients.