Abstract
Rationale: Nitric oxide (NO) exerts an important role in temporally and spatially match microvascular O2 delivery (Q´O2mv) to utilization in the skeletal muscle. Objective: To investigate the effects of increased nitric oxide (NO) bioavailability induced by sildenafil intake on muscle Q´O2mv–to-oxygen uptake (V´O2) matching at the transition to and from exercise in patients with chronic heart failure (CHF). Methods: 10 males (ejection fraction= 27 ± 6 %) underwent a supra-gas exchange threshold exercise test to the limit of tolerance 1 hour after sildenafil (50 mg) or placebo intake. The dynamics of V´O2, fractional O2 extraction in the vastus lateralis (∼ [deoxy-Hb+Mb] by near infrared spectroscopy), and cardiac output (CO) were evaluated by non-linear regression procedures. Results: Sildenafil increased exercise endurance compared to placebo by ∼ 20 %, an effect that was related to faster on- and off-exercise V´O2 kinetics (p<0.05). Active treatment, however, failed to accelerate CO dynamics (p>0.05). On-exercise [deoxy-Hb+Mb] kinetics were slowed by sildenafil with a subsequent response “overshoot” being significantly lessened or even abolished. In contrast, [deoxy-Hb+Mb] recovery was faster with sildenafil (∼ 15 %). Improvements in muscle oxygenation with sildenafil were closely related to faster on-exercise V´O2 kinetics and greater increases in exercise capacity (p<0.05). Conclusions: Sildenafil intake enhanced on- and off-exercise Q´O2mv-to- V´O2 matching and V´O2 kinetics with positive consequences on exercise tolerance in CHF. The lack of effect on CO suggests that improvement in blood flow to and within skeletal muscles underlies these effects.
- © 2012 ERS