Sildenafil improves microvascular O-2 delivery-to-utilization matching and accelerates exercise O-2 uptake kinetics in chronic heart failure

Sperandio, Priscila Abreu [UNIFESP]; Oliveira, Mayron Faria de [UNIFESP]; Rodrigues, Miguel Koite [UNIFESP]; Berton, Danilo Cortozi [UNIFESP]; Treptow, Erika [UNIFESP]; Nery, Luiz Eduardo [UNIFESP]; Almeida, Dirceu Rodrigues de [UNIFESP]; Neder, Jose Alberto [UNIFESP]

Sildenafil improves microvascular O-2 delivery-to-utilization matching and accelerates exercise O-2 uptake kinetics in chronic heart failure

Data

2012-12-01

Autores

Sperandio, Priscila Abreu

Oliveira, Mayron Faria de

Rodrigues, Miguel Koite

Berton, Danilo Cortozi

Treptow, Erika

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Tipo

Artigo

Resumo

Nitric oxide (NO) can temporally and spatially match microvascular oxygen (O-2) delivery (QO(2mv)) to O-2 uptake (VO2) 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 VO2 kinetics, 10 males with CHF (ejection fraction = 27 +/- 6%) undertook constant work-rate exercise (70-80% peak). Breath-by-breath VO2, fractional O-2 extraction in the vastus lateralis {similar to deoxy-genated 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 similar to 20%, an effect that was related to faster on-and off-exercise VO2 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 (similar to 25%), and a subsequent response overshoot (n = 8) was significantly lessened or even abolished. in contrast, [deoxy-Hb + Mb] recovery was faster with sildenafil (similar to 15%). Improvements in muscle oxygenation with sildenafil were related to faster on-exercise VO2 kinetics, blunted oscillations in ventilation (n = 9), and greater exercise capacity (P < 0.05). Sildenafil intake enhanced intramuscular QO(2mv)-to-VO2 matching with beneficial effects on VO2 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.

Citação

American Journal of Physiology-heart and Circulatory Physiology. Bethesda: Amer Physiological Soc, v. 303, n. 12, p. H1474-H1480, 2012.