title: Sildenafil improves microvascular O2 delivery-to-utilization matching and accelerates exercise O2 uptake kinetics in chronic heart failure.
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). Active treatment, however, failed to accelerate CO dynamics (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.
authors.affiliation: Pulmonary Function and Clinical Exercise Physiology Unit, Division of Respiratory Diseases, Department of Medicine, Federal University of São Paulo, Brazil.
authors.forename: Priscila A
authors.initials: PA
authors.lastname: Sperandio
authors.forename: Mayron F
authors.initials: MF
authors.lastname: Oliveira
authors.forename: Miguel K
authors.initials: MK
authors.lastname: Rodrigues
authors.forename: Danilo C
authors.initials: DC
authors.lastname: Berton
authors.forename: Erika
authors.initials: E
authors.lastname: Treptow
authors.forename: Luiz E
authors.initials: LE
authors.lastname: Nery
authors.forename: Dirceu R
authors.initials: DR
authors.lastname: Almeida
authors.forename: J Alberto
authors.initials: JA
authors.lastname: Neder
mesh_terms: D000368:Aged; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D011446:Prospective Studies; D011687:Purines / Q000494:pharmacology; D012039:Regional Blood Flow / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D010100:Oxygen