title: Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker Muscular Dystrophy.
abstract: Patients suffering from Becker muscular dystrophy (BMD) have dysfunctional dystrophin proteins and are deficient in neuronal nitric oxide synthase (nNOS) in muscles. This causes functional ischemia and contributes to muscle wasting. Similar functional ischemia may be present in brains of patients with BMD, who often have mild cognitive impairment, and nNOS may be important for the regulation of the microvascular circulation in the brain. We hypothesized that treatment with sildenafil, a phosphodiesterase type 5 inhibitor that potentiates nitric oxide responses, would augment both the blood oxygen level-dependent (BOLD) response and cerebral blood flow (CBF) in patients with BMD. Seventeen patients (mean ± SD age 38.5 ± 10.8 years) with BMD were included in this randomized, double-blind, placebo-controlled, crossover trial. Twelve patients completed the entire study. Effects of sildenafil were assessed by 3 T magnetic resonance (MR) scanning, evoked potentials, somatosensory task-induced BOLD functional MR imaging, regional and global perfusion, and angiography before and after 4 weeks of sildenafil, 20 mg (Revatio in gelatine capsules, oral, 3 times daily), or placebo treatment. Sildenafil increased the event-related sensory and visual BOLD response compared with placebo (p < 0.01). However, sildenafil did not alter CBF, measured by MR phase contrast mapping, or the arterial diameter of the middle cerebral artery, measured by MR angiography. We conclude that nNOS may play a role in event-related neurovascular responses. Further studies in patients with BMD may help clarify the roles of dystrophin and nNOS in neurovascular coupling in general, and in patients with BMD in particular.
authors.affiliation: Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark.|Lundbeck Foundation Center for Neurovascular signalling (LUCENS), Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lindberg
authors.affiliation: Copenhagen Neuromuscular Center and Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nanna
authors.initials: N
authors.lastname: Witting
authors.affiliation: Lundbeck Foundation Center for Neurovascular signalling (LUCENS), Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark.
authors.forename: Stine Lundgaard
authors.initials: SL
authors.lastname: Jørgensen
authors.affiliation: Copenhagen Neuromuscular Center and Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: John
authors.initials: J
authors.lastname: Vissing
authors.affiliation: Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark.
authors.forename: Egill
authors.initials: E
authors.lastname: Rostrup
authors.affiliation: Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark.|Lundbeck Foundation Center for Neurovascular signalling (LUCENS), Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark.
authors.forename: Henrik Bo Wiberg
authors.initials: HB
authors.lastname: Larsson
authors.affiliation: Lundbeck Foundation Center for Neurovascular signalling (LUCENS), Rigshospitalet Glostrup, University of Copenhagen, Glostrup, Denmark. ckruuse@dadlnet.dk.|Neurovascular Research Unit, Department of Neurology, Herlev Gentofte Hospital, University of Copenhagen, Herlev, Denmark. ckruuse@dadlnet.dk.
authors.forename: Christina
authors.initials: C
authors.lastname: Kruuse
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology*; D001931:Brain Mapping; D004311:Double-Blind Method; D006801:Humans; D006935:Hypercapnia / Q000000981:diagnostic imaging / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D020388:Muscular Dystrophy, Duchenne / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010812:Physical Stimulation; D011597:Psychomotor Performance; D000068677:Sildenafil Citrate / Q000008:administration & dosage / Q000627:therapeutic use*; D055698:Touch Perception / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate
keywords: Becker muscular dystrophy; EEG; Neurovascular coupling; Sildenafil; fMRI