What is the clinical evidence from this study?

Study design: RCT. Population: Chronic heart failure (n=10). Intervention: Sildenafil vs. Placebo. Primary outcome: Exercise tolerance (~20% increase, p=<0.05).

What does this research mean for the field?

Sildenafil (50 mg) increases exercise tolerance by approximately 20% in males with chronic heart failure, an effect driven by enhanced intramuscular oxygen delivery-to-utilization matching and faster oxygen uptake kinetics rather than changes in cardiac output. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

October 1, 2012Open Access

Sildenafil improves microvascular O2 delivery-to-utilization matching and accelerates exercise O2 uptake kinetics in chronic heart failure

Q: What are the key findings of this study?

Sildenafil (50 mg) increased exercise tolerance by ~20% compared with placebo in males with chronic heart failure, an effect related to faster on- and off-exercise Vo2 kinetics (P < 0.05).

Q: What does this research mean for the field?

Sildenafil (50 mg) increases exercise tolerance by approximately 20% in males with chronic heart failure, an effect driven by enhanced intramuscular oxygen delivery-to-utilization matching and faster oxygen uptake kinetics rather than changes in cardiac output. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

Sildenafil (50 mg) increased exercise tolerance by ~20% compared with placebo in males with chronic heart failure, an effect related to faster on- and off-exercise Vo2 kinetics (P < 0.05).

Study Design

Type

RCT (n=10)

Structured PICO

Does sildenafil improve muscle oxygen delivery-to-utilization matching and exercise tolerance in males with chronic heart failure?

Population

10 males with chronic heart failure (CHF), ejection fraction = 27 ± 6%

Intervention

Sildenafil 50 mg

Comparator

Placebo

Outcome

Muscle Qo2mv-to-O2 utilization matching, Vo2 kinetics, fractional O2 extraction in the vastus lateralis, and cardiac output during constant work-rate exercise (70-80% peak)surrogate

Sildenafil acutely improves exercise tolerance and oxygen uptake kinetics in men with chronic heart failure, likely via enhanced skeletal muscle blood flow rather than increased cardiac output.

Main Result

Effect estimate: ~20% increase

p-value: p=<0.05

Abstract

Nitric oxide (NO) can temporally and spatially match microvascular oxygen (O (2) ) delivery (Qo (2mv) ) to O (2) uptake (Vo (2) ) in the skeletal muscle, a crucial adjustment-to-exercise tolerance that is impaired in chronic heart failure (CHF). To investigate the effects of NO bioavailability induced by sildenafil intake on muscle Qo (2mv) -to-O (2) utilization matching and Vo (2) kinetics, 10 males with CHF (ejection fraction = 27 ± 6%) undertook constant work-rate exercise (70-80% peak). Breath-by-breath Vo (2), fractional O (2) extraction in the vastus lateralis ∼deoxygenated hemoglobin + myoglobin (deoxy-Hb + Mb) by near-infrared spectroscopy, and cardiac output (CO) were evaluated after sildenafil (50 mg) or placebo. Sildenafil increased exercise tolerance compared with placebo by ∼20%, an effect that was related to faster on- and off-exercise Vo (2) kinetics (P 0. 05). On-exercise deoxy-Hb + Mb kinetics were slowed by sildenafil (∼25%), and a subsequent response "overshoot" (n = 8) was significantly lessened or even abolished. In contrast, deoxy-Hb + Mb recovery was faster with sildenafil (∼15%). Improvements in muscle oxygenation with sildenafil were related to faster on-exercise Vo (2) kinetics, blunted oscillations in ventilation (n = 9), and greater exercise capacity (P < 0. 05). Sildenafil intake enhanced intramuscular Qo (2mv) -to-Vo (2) matching with beneficial effects on Vo (2) kinetics and exercise tolerance in CHF. The lack of effect on CO suggests that improvement in blood flow to and within skeletal muscles underlies these effects.