Exercise Training Reverses Extrapulmonary Impairments in Smoke-exposed Mice.

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 non-pharmacological treatments such as exercise training. Methods: Three groups of mice including control (n=10), smoking (n=10), and smoking with 6 weeks of high-intensity interval treadmill running (n=11) were exposed to 20 weeks of fresh air or whole-body cigarette smoke. Exercise capacity (peak oxygen uptake) and lung destruction (histology) were subsequently measured, while 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% (P0.05). 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

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