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 αB-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 low-load 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 (O'Neill et al. 2006). Upon exercise stress, the recruitment of specific motor units may lead to increased Hsp expression or translocation in recruited muscle fibres (Paulsen et al. 2007, Noble et al. 2008). In addressing the issue of whether low-load resistance exercise under partial BFR results in recruitment of high-threshold type II fibres, Cumming et al. examined glycogen depletion patterns in vastus lateralis muscle biopsy cross-sections. They observed that type I and type II fibres both exhibited reduced glycogen content in each of the BFR and free-flow legs but that there was a greater glycogen depletion in the BFR leg. Reduced glycogen staining was also observed at an earlier time post-exercise in the BFR leg, particularly in type II fibres. These data suggest that both type I and type II fibres were recruited with low-load resistance exercise, particularly with BFR. When the heat shock response in different fibre types was examined, type I fibres exhibited an increased staining intensity for both αB-crystallin and Hsp70, particularly after BFR, whereas changes in Hsp staining intensity in type II fibres were minimal and did not differ between legs. This pattern of fibre-type staining specificity is different from that observed with damaging, high-load eccentric muscle contractions. The latter type of contraction leads to a greater increase in Hsp expression in type II fibres with a more punctate distribution (Paulsen et al. 2009). Overall, these data suggest that despite the apparent greater recruitment of type II fibres with low-load resistance exercise, particularly with BFR, that type II fibres did not undergo significant stress in response to exercise. Alternatively, similar to observations in rat plantaris muscle following functional overload, type IIx fibres may be somewhat refractory to the heat shock response (O'Neill et al. 2006). In this study, type II fibres were not subcategorized; hence, a resolution of these options awaits further experimentation. An interesting observation raised by Cumming et al. was that Hsp70 content was highest in those fibres with the lowest glycogen content 48 h post-exercise. As Hsp70 has been shown to be intimately involved in insulin signalling and subsequent glucose transport (Chung et al. 2008), the observed elevation in Hsp70 in these glycogen-depleted fibres may represent an effort to restore metabolic homeostasis. In summary, based upon an examination of the translocation and expression of Hsps in human vastus lateralis muscle, Cumming et al. have provided interesting data demonstrating that cytoskeletal proteins are stressed during blood-flow-restricted low-load resistance exercise. The damage is not overt, as that observed during more strenuous eccentric exercise, but combined with previous observations that this type of exercise may lead to muscle hypertrophy, this does not discount the popular notion that some myofibrillar damage or stress may be required to initiate muscle growth. Coupled with glycogen depletion patterns in individual fibre types, their data also suggest that higher threshold, type II muscle fibres are recruited with BFR low-load resistance exercise but that the overall stress placed on them is minimal compared to that of type I fibres or under more demanding eccentric conditions. This could have consequences for the hypertrophic potential of these type II fibres under these exercise conditions. Lastly, despite the fact that changes in both Hsp27 and αB-crystallin in the BFR leg were associated with force deficits, our understanding of the exact role of these proteins within the cell following exercise stress is limited. Based upon the translocation of Hsps to the cytoskeleton, it is likely that they are playing a role in protecting myofibrillar proteins from exercise-induced damage, but the mechanisms underlying this protection are unclear and await further investigation. The effects of BFR low-load resistance exercise in trained as opposed to the naive subjects used in this study also represent future queries. I do not have any conflict of interest.

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