Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker Muscular Dystrophy
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Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker Muscular Dystrophy. / Lindberg, Ulrich; Witting, Nanna; Jørgensen, Stine Lundgaard; Vissing, John; Rostrup, Egill; Larsson, Henrik Bo Wiberg; Kruuse, Christina.
I: Neurotherapeutics, Bind 14, Nr. 1, 01.2017, s. 182-190.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker Muscular Dystrophy
AU - Lindberg, Ulrich
AU - Witting, Nanna
AU - Jørgensen, Stine Lundgaard
AU - Vissing, John
AU - Rostrup, Egill
AU - Larsson, Henrik Bo Wiberg
AU - Kruuse, Christina
PY - 2017/1
Y1 - 2017/1
N2 - 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.
AB - 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.
KW - Adult
KW - Brain/blood supply
KW - Brain Mapping
KW - Double-Blind Method
KW - Humans
KW - Hypercapnia/diagnostic imaging
KW - Magnetic Resonance Imaging
KW - Middle Aged
KW - Muscular Dystrophy, Duchenne/diagnostic imaging
KW - Phosphodiesterase 5 Inhibitors/administration & dosage
KW - Physical Stimulation
KW - Psychomotor Performance
KW - Sildenafil Citrate/administration & dosage
KW - Touch Perception/physiology
KW - Treatment Outcome
U2 - 10.1007/s13311-016-0467-x
DO - 10.1007/s13311-016-0467-x
M3 - Journal article
C2 - 27485237
VL - 14
SP - 182
EP - 190
JO - Neurotherapeutics
JF - Neurotherapeutics
SN - 1933-7213
IS - 1
ER -
ID: 193273551