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Title: Sildenafil improves microvascular O-2 delivery-to-utilization matching and accelerates exercise O-2 uptake kinetics in chronic heart failure
Authors: Sperandio, Priscila A. [UNIFESP]
Oliveira, Mayron F. [UNIFESP]
Rodrigues, Miguel K. [UNIFESP]
Berton, Danilo C. [UNIFESP]
Treptow, Erika [UNIFESP]
Nery, Luiz E. [UNIFESP]
Almeida, Dirceu R. [UNIFESP]
Neder, J. Alberto [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Queens Univ
Keywords: sildenafil
blood flow
heart failure
near-infrared spectroscopy
oxygen consumption
Issue Date: 1-Dec-2012
Publisher: Amer Physiological Soc
Citation: American Journal of Physiology-heart and Circulatory Physiology. Bethesda: Amer Physiological Soc, v. 303, n. 12, p. H1474-H1480, 2012.
Abstract: Sperandio PA, Oliveira MF, Rodrigues MK, Berton DC, Treptow E, Nery LE, Almeida DR, Neder JA. Sildenafil improves microvascular O-2 delivery-to-utilization matching and accelerates exercise O-2 uptake kinetics in chronic heart failure. Am J Physiol Heart Circ Physiol 303: H1474-H1480, 2012. First published September 28, 2012; doi:10.1152/ajpheart.00435.2012.-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.
ISSN: 0363-6135
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