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Exercise Training Reverses Extrapulmonary Impairments in Smoke-exposed Mice

BOWEN, T. SCOTT; AAKERØY, LARS; EISENKOLB, SOPHIA; KUNTH, PATRICIA; BAKKERUD, FREDRIK; WOHLWEND, MARTIN; ORMBOSTAD, ANNE MARIE; FISCHER, TINA; WISLOFF, ULRIK; SCHULER, GERHARD; STEINSHAMN, SIGURD; ADAMS, VOLKER; BRONSTAD, EIVIND

Medicine & Science in Sports & Exercise: May 2017 - Volume 49 - Issue 5 - p 879–887
doi: 10.1249/MSS.0000000000001195
Basic Sciences

Purpose: Cigarette smoking is the main risk factor for chronic obstructive pulmonary disease and emphysema. However, evidence on the extrapulmonary effects of smoke exposure that precede lung impairments remains unclear at present, as are data on nonpharmacological treatments such as exercise training.

Methods: Three groups of mice, including control (n = 10), smoking (n = 10), and smoking with 6 wk of high-intensity interval treadmill running (n = 11), were exposed to 20 wk of fresh air or whole-body cigarette smoke. Exercise capacity (peak oxygen uptake) and lung destruction (histology) were subsequently measured, whereas the heart, peripheral endothelium (aorta), and respiratory (diaphragm) and limb (extensor digitorum longus and soleus) skeletal muscles were assessed for in vivo and in vitro function, in situ mitochondrial respiration, and molecular alterations.

Results: Smoking reduced body weight by 26% (P < 0.05) without overt airway destruction (P > 0.05). Smoking impaired exercise capacity by 15% while inducing right ventricular dysfunction by ~20%, endothelial dysfunction by ~20%, and diaphragm muscle weakness by ~15% (all P < 0.05), but these were either attenuated or reversed by exercise training (P < 0.05). Compared with controls, smoking mice had normal limb muscle and mitochondrial function (cardiac and skeletal muscle fibers); however, diaphragm measures of oxidative stress and protein degradation were increased by 111% and 65%, respectively (P < 0.05), but these were attenuated by exercise training (P < 0.05).

Conclusions: Prolonged cigarette smoking reduced exercise capacity concomitant with functional impairments to the heart, peripheral endothelium, and respiratory muscle that preceded the development of overt emphysema. However, high-intensity exercise training was able to reverse these smoke-induced extrapulmonary impairments.

1Department of Internal Medicine and Cardiology, Leipzig University–Heart Center, Leipzig, GERMANY; 2Faculty of Medicine, Department of Circulation and Medical Imaging, K.G. Jebsen Center of Exercise in Medicine, Norwegian University of Science and Technology, Trondheim, NORWAY; and 3Department of Thoracic Medicine, Clinic of Thoracic and Occupational Medicine, St. Olav's University Hospital, Trondheim, NORWAY

Address for correspondence: T Scott Bowen, Ph.D., University of Leipzig–Heart Center, Strümpellstrasse 39, 04289 Leipzig, Germany; E-mail: bows@med.uni-leipzig.de.

T. S. B and L. A. contributed equally in this study.

Submitted for publication September 2016.

Accepted for publication December 2016.

© 2017 American College of Sports Medicine