Exercise Intolerance in Cystic Fibrosis: Importance of Skeletal Muscle

Purpose Exercise intolerance, evaluated by O-2 consumption, predicts mortality in cystic fibrosis (CF). People with CF exhibit skeletal muscle dysfunctions that may contribute to an imbalance between O-2 delivery and utilization. Sildenafil, a phosphodiesterase type 5 inhibitor, increases blood flow and improves O-2 consumption, although the exact mechanisms in CF have yet to be elucidated. Thus, we hypothesized that exercise intolerance in CF is limited primarily by an impaired skeletal muscle O-2 utilization, and sildenafil improves exercise tolerance in CF by addressing this mismatch between O-2 demand and extraction. Methods Fifteen individuals with mild to moderate CF and 18 healthy controls completed an incremental exercise test and measurements of gaseous exchange, chronotropic response, hemodynamics, and O-2 extraction and utilization. People with CF also completed a 4-wk treatment with sildenafil with a subsequent follow-up evaluation after treatment. Results Skeletal muscle O-2 extraction and utilization during exercise were reduced in people with CF when compared with controls. Exercise capacity in our CF population was minimally limited by hemodynamic or chronotopic responses, whereas peripheral O-2 extraction was more closely associated with exercise capacity. The study also demonstrated that 4 wk of sildenafil improved skeletal muscle O-2 utilization during exercise to similar values observed in healthy individuals. Conclusions Individuals with mild to moderate CF exhibit exercise intolerance secondary to a reduction in O-2 utilization by the exercising skeletal muscle. The present study demonstrated that 4 wk of sildenafil treatment improves the capacity of the skeletal muscle to use O-2 more efficiently during exercise. Findings from the present study highlight the importance of targeting skeletal muscle O-2 utilization to improve exercise tolerance in CF.