Estudo do sildenafil na função muscular e cardíaca na distrofia muscular de Becker
Dinamarca – estudos experimentais demonstraram que o sildenafil, indicado para disfunção erétil, pode melhorar a força muscular, melhorar a oxigenação dos músculos, melhorar a função cardíaca entre outras ações. Nesta pesquisa 16 pacientes com Becker foram tratados com sildenafil e não apresentaram nenhuma melhora tanto na força muscular quanto na função cardíaca. Os pacientes não apresentaram efeitos colaterais.
O resumo em inglês do artigo pode ser lido abaixo:
(Annals of Neurology, 2014) Effect of sildenafil on skeletal and cardiac muscle in Becker muscular dystrophy
N Witting, C Kruuse, B Nyhuus, KP Prahm, G Citirak, SJ Lundgaard, S von Huth, N Vejlstrup, U Lindberg, TO Krag and J Vissing – Dennark
Background; patients with Becker and Duchenne muscular dystrophies, (BMD and DMD) 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 randomised, double-blind, placebo-controlled crossover design with two 4-week periods of treatment, separated by 2-week wash-out was used. We assessed brachial artery blood flow during maximal handgrip exercise, six minutes walk test, maximal oxidative capacity, life quality, and cardiac function was evaluated by MRI at rest and during maximal handgrip exercise. Muscle nNOS and PDE5 was tested with western blotting in 5 patients
Findings; sixteen patients completed all skeletal muscle evaluations and 13 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 5/5 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 down-regulation of PDE5 in muscle.
