Exercise and Muscular Dystrophy: Implications and Analysis of Effects on Musculoskeletal and Cardiovascular Systems

Abstract

The muscular dystrophies are a heterogeneous collection of progressive, inherited diseases of muscle weakness and degeneration. Although these diseases can vary widely in their etiology and presentation, nearly all muscular dystrophies cause exercise intolerance to some degree. Here, we focus on Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophy, as a paradigm for the effects of muscle disease on exercise capacity. First described in the mid-1800s, DMD is a rapidly progressive and lethal muscular dystrophy caused by mutations in the dystrophin gene. Dystrophin is a membrane-associated cytoskeletal protein, the loss of which causes numerous cellular defects including mechanical instability of the sarcolemma, increased influx of extracellular calcium, and cell signaling defects. Here, we discuss the physiological basis for exercise intolerance in DMD, focusing on the molecular and cellular defects caused by loss of dystrophin and how these manifest as organ-level dysfunction and reduced exercise capacity. The main focus of this article is the defects present in dystrophin-deficient striated muscle. However, discussion regarding the effects of dystrophin loss on other tissues, including vascular smooth muscle is also included. Collectively, the goal of this article is to summarize the current state of knowledge regarding the mechanistic basis for exercise intolerance in DMD, which may serve as an archetype for other muscular dystrophies and diseases of muscle wasting.

Comparison of Experimental Protocols of Physical Exercise for mdx Mice and Duchenne Muscular Dystrophy Patients

“…The five mechanisms rendering dystrophin-deficient muscles vulnerable to exercise (reviewed elsewhere [12]) are the weakening of the sarcolemma, increased calcium influx and oxidative stress, recurrent muscle ischemia and aberrant signalling to surrounding tissues such as nerves or cells of the immune system. A mechanistic basis for exercise intolerance [13] and recommendations for the management of DMD [9, 14] have also been reviewed. The lack of uniformity between protocols for exercise of dystrophin-deficient muscles, however, has been pointed out [15], but not reviewed.…”

Low Intensity Training Provokes Adaptations on Muscle Fibrosis of a Muscular Dystrophy Model

“…Also, at this age there is an already described similarity of fibrosis and muscular deterioration between humans and mdx mice age-matched. See schematic Figure 1 plotted with these similarities between both species according to the literature (Briguet et al;Grounds et al, 2008;Barnabei et al, 2011;Hyzewicz et al, 2015). This research was approved by the Ethics Committee on Animal Use of the University Federal dos Vales do Jequitinhonha e Mucuri (CEUA/UFVJM), protocol number 017/2011.…”

A Multidisciplinary Perspective Addressing the Diagnostic Challenges of Late-Onset Pompe Disease in the Arabian Peninsula Region Developed From an Expert Group Meeting

“…The other clinical manifestations are ptosis, brain aneurysms, arrhythmias, facial muscle weakness, dysphagia, dysarthria, a rigid spine, and macroglossia [13]. The symptoms of LOPD may mimic that of other diseases, including unspecified myopathy, limb-girdle muscular dystrophy, and inflammatory myopathy [9,[14][15][16][17][18][19][20][21][22][23][24]. This broad clinical spectrum of manifestations that mimic symptoms of other diseases is a significant barrier that hinders initial diagnosis and thereby causes diagnostic delays.…”