Is blood‐flow‐restricted low‐load resistance exercise really stress free?

Recently, there has been considerable interest in the use of blood-flow-restricted (BFR) low-load resistance exercise to induce muscle hypertrophy. This training method is purported to initiate muscle growth in the absence of the muscle damage and stress, which normally accompanies traditional high-load, high-intensity resistance exercise (Takarada et al. 2000) As such, it could be a valuable method to maintain or enhance muscle strength for certain clinical or aging populations and in some rehabilitation situations. In this issue, the article by Cumming et al. (2014) uses the sensitivity of the exercise-induced heat shock response to examine two questions in the literature surrounding BFR low-load resistance exercise. First, it has long been believed that muscle damage accompanying resistance training is a primary factor associated with the initiation of skeletal muscle hypertrophy (Evans & Cannon 1991). Heavier loads and in particular exercise involving eccentric muscle contractions not only induce overt muscle damage but can maximally activate all muscle fibres, resulting in significant hypertrophy. However, whether such damage is a prerequisite for muscle growth has been questioned (Flann et al. 2011) as BFR low-load training leads to muscle hypertrophy without apparent muscle damage (Takarada et al. 2000). There is controversy around this observation, however, particularly in naive subjects (Umbel et al. 2009). Secondly, one of the supposed attributes of BFR exercise is that it leads to muscle hypertrophy by enabling the recruitment of higher threshold, type II motor units at a lower load than under traditional resistance training procedures. However, this conclusion has been drawn largely from studies conducted with complete ischaemia (Krustrup et al. 2009). The muscle fibre recruitment pattern with the more frequently used partial ischaemia or low-flow model is less clear. To address these issues, Cumming et al. had subjects perform five sets of single-legged, knee extensions at 30% of their one repetition maximum. With the experimental leg, subjects exercised to failure under partial BFR induced by an inflated blood pressure cuff surrounding the proximal thigh. The other free-flow leg performed the same number of repetitions at the same load but without BFR. Muscle biopsies from the vastus lateralis muscle were taken pre-exercise and at 1, 24 and 48 h post-exercise for analysis of heat shock protein (Hsp) content, translocation and fibre-specific distribution. Heat shock proteins represent primordial proteins which act as a superfamily to protect organisms from stressful conditions. They are grouped according to molecular weight, and individual proteins within these groups tend to have slightly different masses and cellular localizations. They are involved primarily in preventing unwanted protein aggregation or activating pathways which lead to cellular survival and the orderly removal of proteins damaged beyond repair (Noble et al. 2008). Damaging eccentric exercise or complete ischaemia is known to lead to increased expression and translocation of Hsps (Golenhofen et al. 2004, Paulsen et al. 2007). The exact role of these Hsps is unknown, but following ischaemia, they have been observed to be tightly bound to proteins in the I-band where they may be involved in protection of titan and actin filaments (Golenhofen et al. 2004). Damaging eccentric exercise leads to a similar pattern of cytoskeletal binding with actin, M-line proteins, titin and intermediate proteins, particularly desmin as potential clients (Paulsen et al. 2007). Hence, these proteins may stabilize and protect these myofilament structures immediately after stress. The observation by Cumming et al. that a translocation of the small heat shock proteins (Hsp27 and aB-crystallin) from cytosolic and membrane fractions to the cytoskeletal fraction occurred within an hour post-exercise has advanced our understanding of the stress placed upon skeletal muscle during BFR lowload resistance exercise. Importantly, as both the BFR and free-flow leg exhibited some translocation, this suggests that even low-load resistance exercise in the absence of BFR is accompanied by stress or damage to specific cytoskeletal components, although not to the same degree as with high-load eccentric exercise. This point was reinforced in that, the inducible isoform of Hsp70 (Hsp70), which may be involved in recovery from stressful exercise, also increased in the cytoskeletal fraction but at a later time post-exercise, particularly in the free-flow leg. The greater and more persistent translocation of the small Hsps observed in the BFR leg suggests that an additional stress beyond exercise, possibly ischaemic or metabolic, was imposed with BFR. Under basal conditions, skeletal muscle exhibits a fibre-specific expression of Hsps, with the small Hsps and Hsp70 being expressed to a greater degree in type I and type IIa fibres than in type IIb or type IIx fibres