Sildenafil Increases Exercise Capacity, Study Suggests

Sildenafil improves how muscles work when patients with cystic fibrosis (CF) exercise and this translates into better exercise capacity, a new study suggests.

The study, “Exercise intolerance in cystic fibrosis: importance of skeletal muscle,” was published in the journal Medicine & Science in Sports & Exercise.

Patients with CF often have exercise intolerance, defined as a decreased ability to perform physical exercise. Exercise intolerance is evaluated by oxygen consumption and has been suggested as a way to predict mortality in CF patients.

Researchers now have hypothesized that exercise intolerance could be due to an imbalance between how much oxygen is delivered to the whole body and how much oxygen is used, or extracted, by the muscles.

“Based on the complicated pathophysiology of CF and the recognized role of muscle O2 [oxygen] extraction on exercise capacity, we hypothesized that when evaluated simultaneously, people with mild to moderate CF would exhibit exercise intolerance that was limited in part by an inability of the skeletal muscle to use O2 efficiently,” the researchers wrote.

To test their hypothesis, the team studied 15 patients with mild-to-moderate CF and 18 healthy individuals as the control group. Their exercise capacity, blood flow dynamics, measures of gas exchange, and oxygen utilization were evaluated at baseline (study start).

As expected, measures of lung function were lower in patients with CF than in healthy individuals. Exercise capacity on a cycle ergometer (stationary bike) and measures of ventilation (the movement of air between the environment and the lungs via inhalation and exhalation) also were lower.

In patients with CF, exercise capacity was found to be limited by the ability of skeletal muscles — the muscles responsible for movement — to extract oxygen.

“Individuals with mild to moderate CF exhibit reduced peripheral O2 extraction during exercise that likely contributes to the observed exercise intolerance,” the researchers wrote.

Sildenafil (marketed by Pfizer under the brand name Revatio) is a phosphodiesterase type 5 (PDE-5) inhibitor that is approved by the U.S. Food and Drug Administration to improve exercise capacity in patients with pulmonary arterial hypertension. Sildenafil works by widening the blood vessels, increasing blood flow and reducing blood pressure.

In a previous study, the researchers had shown that taking sildenafil for four weeks improved exercise capacity in patients with CF. Now, the team hypothesized that sildenafil could improve exercise capacity by addressing the imbalance between oxygen delivery and extraction.

To test this, the 15 CF patients took sildenafil (20 milligrams, three times a day) in addition to their standard CF therapy for four weeks. After that period all patients performed new lung function and exercise capacity tests.

Results showed that taking sildenafil for four weeks did not improve lung function. However, as in the previous study, it did increase exercise capacity by an average of 4.7%.

The increase in exercise capacity was accompanied by increases in ventilation and oxygen extraction by the skeletal muscles, with values reaching those of control participants.

Based on the results, the team concluded that “individuals with mild to moderate CF exhibit exercise intolerance secondary to a reduction in O2 utilization by the exercising skeletal muscle,” they wrote, adding that the data also “demonstrated that [four weeks] of sildenafil treatment improves the capacity of the skeletal muscle to use O2 more efficiently during exercise.”

“Taken together, our findings highlight the importance of targeting mechanisms of skeletal muscle O2 utilization in CF to augment exercise tolerance and the therapeutic potential of sildenafil,” they concluded.