Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Effect of sildenafil on skeletal and cardiac muscle in Becker muscular dystrophy

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Autism and developmental disability caused by KCNQ3 gain-of-function variants

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Residual Descending Motor Pathways Influence Spasticity after Spinal Cord Injury

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Disease progression and outcome measures in spinobulbar muscular atrophy

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Plasma urate and risk of Parkinson's disease: A mendelian randomization study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Hydroxylated Long-Chain Acylcarnitines are Biomarkers of Mitochondrial Myopathy

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. MSTO1 mutations cause mtDNA depletion, manifesting as muscular dystrophy with cerebellar involvement

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Growth and differentiation factor 15 as a biomarker for mitochondrial myopathy

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Palbociclib in combination with simvastatin induce severe rhabdomyolysis: a case report

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

OBJECTIVE: Patients with Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy lack neuronal nitric oxide synthase (nNOS). nNOS mediates physiological sympatholysis, thus ensuring adequate blood supply to working muscle. In mice lacking dystrophin, restoration of nNOS effects by a phosphodiesterase 5 (PDE5) inhibitor (sildenafil) improves skeletal and cardiac muscle performance. Sildenafil also improves blood flow in patients with BMD. We therefore hypothesized that sildenafil would improve blood flow, maximal work capacity, and heart function in patients with BMD.

METHODS: A randomized, double-blind, placebo-controlled crossover design with two 4-week periods of treatment, separated by 2-week washout was used. We assessed brachial artery blood flow during maximal handgrip exercise, 6-minute walk test, maximal oxidative capacity, and life quality; cardiac function was evaluated by magnetic resonance imaging (MRI) at rest and during maximal handgrip exercise. Muscle nNOS and PDE5 were tested with Western blotting in 5 patients.

RESULTS: Sixteen patients completed all skeletal muscle evaluations, and 13 completed the cardiac MRI investigations. Sildenafil had no effect on any of the outcome parameters. No serious adverse effects were recorded. PDE5 and nNOS were deficient in 5 of 5 biopsies.

INTERPRETATION: Despite positive evidence from animal models of dystrophinopathy and physiological findings in patients with BMD, this double-blind, placebo-controlled clinical study showed no effect of sildenafil on blood flow, maximal work capacity, and heart function in adults with BMD. This discrepancy may be explained by a significant downregulation of PDE5 in muscle.

OriginalsprogEngelsk
TidsskriftAnnals of Neurology
Vol/bind76
Udgave nummer4
Sider (fra-til)550-7
Antal sider8
ISSN0364-5134
DOI
StatusUdgivet - 2014

ID: 44932288