Neurotherapeutics

, Volume 14, Issue 1, pp 182–190

Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker Muscular Dystrophy

  • Ulrich Lindberg
  • Nanna Witting
  • Stine Lundgaard Jørgensen
  • John Vissing
  • Egill Rostrup
  • Henrik Bo Wiberg Larsson
  • Christina Kruuse
Original Article

DOI: 10.1007/s13311-016-0467-x

Cite this article as:
Lindberg, U., Witting, N., Jørgensen, S.L. et al. Neurotherapeutics (2017) 14: 182. doi:10.1007/s13311-016-0467-x

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.

Keywords

Becker muscular dystrophy fMRI EEG Sildenafil Neurovascular coupling 

Supplementary material

13311_2016_467_MOESM1_ESM.pdf (1.2 mb)
Required Author Forms Disclosure forms provided by the authors are available with the online version of this article. (PDF 1224 kb)
13311_2016_467_MOESM2_ESM.doc (103 kb)
Appendix S1Detailed overview of the important parameters for all magnetic resonance imaging scans (DOC 103 kb)

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2016

Authors and Affiliations

  • Ulrich Lindberg
    • 1
    • 2
  • Nanna Witting
    • 3
  • Stine Lundgaard Jørgensen
    • 2
  • John Vissing
    • 3
  • Egill Rostrup
    • 1
  • Henrik Bo Wiberg Larsson
    • 1
    • 2
  • Christina Kruuse
    • 2
    • 4
  1. 1.Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet GlostrupUniversity of CopenhagenGlostrupDenmark
  2. 2.Lundbeck Foundation Center for Neurovascular signalling (LUCENS), Rigshospitalet GlostrupUniversity of CopenhagenGlostrupDenmark
  3. 3.Copenhagen Neuromuscular Center and Department of Neurology, RigshospitaletUniversity of CopenhagenCopenhagenDenmark
  4. 4.Neurovascular Research Unit, Department of Neurology, Herlev Gentofte HospitalUniversity of CopenhagenHerlevDenmark

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