Exercise Intolerance in Cystic Fibrosis: Importance of Skeletal Muscle

Abstract

Purpose 

Exercise intolerance, evaluated by O₂ consumption, predicts mortality in cystic fibrosis (CF). People with CF exhibit skeletal muscle dysfunctions that may contribute to an imbalance between O₂ delivery and utilization. Sildenafil, a phosphodiesterase type 5 inhibitor, increases blood flow and improves O₂ 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 O₂ utilization, and sildenafil improves exercise tolerance in CF by addressing this mismatch between O₂ 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 O₂ 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 O₂ 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 O₂ extraction was more closely associated with exercise capacity. The study also demonstrated that 4 wk of sildenafil improved skeletal muscle O₂ 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 O₂ 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 O₂ more efficiently during exercise. Findings from the present study highlight the importance of targeting skeletal muscle O₂ utilization to improve exercise tolerance in CF.