Acute blood flow restricted exercise to treat Duchenne muscular dystrophy: would it be efficacious?

Abstract

The most common form of muscular dystrophy is Duchenne muscular dystrophy (DMD), which is an X-linked disorder affecting 1 in 3500 newborn males across the world. DMD is caused by the lack of dystrophin which is a protein that provides stability to the sarcolemma and is likely involved in the transmission of force between the extracellular matrix and the intracellcular contractile apparatus (Lovering and Brooks, 2013). Due to the absence of this protein, the sarcolemma is easily damaged in response to muscle contraction (Markert et al., 2012). Although there is no cure for DMD, exercise has been proposed as a possible treatment; however, the risk of muscle damage is a large concern for this population (Markert et al., 2012). Therefore, traditional strength training which includes high load eccentric contractions may need to be avoided in patients with DMD due to the susceptibility of muscle damage with lengthening contractions. In addition, although submaximal exercise may exert some benefits for this population, the low load exercise is unlikely to be an optimal stimulus for maintaining or increasing muscle function. Interestingly, there are numerous studies (>40) in healthy subjects which suggest that submaximal exercise in combination with blood flow restriction (BFR) can elicit muscle adaptations similar to that observed with higher load resistance training (Loenneke et al., 2012c) without increasing indices of muscle damage (Loenneke et al., 2011). Briefly, BFR is a stimulus commonly applied with specialized pressure cuffs placed at the top of a limb which are inflated to a set pressure throughout exercise. The pressure applied should be high enough to occlude venous return from the muscle but low enough to maintain arterial inflow into the muscle. Available evidence indicates that the pressure applied should be based on the size of the limb (i.e., bigger the limb higher the pressure) (Loenneke et al., 2012b). The proposed mechanisms (Loenneke et al., 2012a) behind the effects of low load exercise in combination with BFR on skeletal muscle include acute muscle cell swelling, increased fiber type recruitment from metabolic accumulation, decreased myostatin (48 h after last training session), decreased atrogenes (8 h post exercise), and the proliferation of satellite cells (8 days into training intervention, 3 and 10 days after cessation of training) (Nielsen et al., 2012). A recent review discussed 5 mechanisms of DMD pathology which may improve or worsen as a result of exercise training which included: (1) mechanical weakening of the sarcolemma; (2) inappropriate calcium influx; (3) aberrant cell signaling (angiogenesis); (4) increased oxidative stress; and (5) recurrent muscle ischemia (Markert et al., 2012). The purpose of this manuscript is to discuss each one of these mechanisms as it relates to what is known about low load resistance exercise in combination with BFR.