UC San Diego

Muscle dysfunction is thought to contribute to exercise intolerance in smokers with chronic obstructive pulmonary disease (COPD). In this study, cigarette smoke (CS) was hypothesized to impair skeletal muscle fatigue resistance via a decrement in vascular function associated with a change in the macrophage cell profile. To test this hypothesis, adult C57Bl/6J mice were exposed, via a nose- only system, to daily periods of CS (5 cigarettes/period for 2 periods, 5 days/week) for 8 weeks and compared to mice delivered CS-extract (weekly, i.p) and control, unexposed mice. A significant difference in fatigue resistance was seen in CS and CS-extract mice [Control: 337 ± 51 sec, CS: 177 ± 17 sec, CS-extract: 177 ± 18 sec, p<0.05)]. Lung air space size was not affected in either of the smoke-exposed groups. A decreased capillary to fiber ratio was observed in the soleus of CS and CS- extract mice [Control: 1.60 ± 0.11, CS: 1.26 ± 0.04, CS- extract: 1.05 ± 0.03 (p<0.05)]. Arterial remodeling, a changing in the number or size of arteries, was not detected in the gastrocnemius complex. Control mice showed a trend of a greater number of M2-polarized macrophages in the gastrocnemius than the CS and CS-extract groups. These data suggest that cigarette smoke components may directly induce muscle dysfunction independent of changes in lung function. Vascular dysfunction at the capillary level, associated with a decrease in pro-angiogenic M2 macrophages, may limit O₂ and nutrient availability during periods of muscle contraction and contribute to poor locomotor skeletal muscle function in smokers