Powers et al. (2013) propose that mechanical ventilation (MV) imposes rapid diaphragm muscle atrophy as a result of inactivity. Their argument is essentially one of exclusion, rather than direct evidence. They argue that MV does not influence circulating inflammatory cytokines or induce sepsis that may be responsible for atrophy. However, they acknowledge that keratinocyte-derived chemokine does increase after MV, although its role in MV-induced atrophy has not been established. The argument dismissing the role of toll-like receptor TLR4 ligands on MV-induced atrophy is hardly evidence for a role of inactivity. They state that the role of inactivity is also supported by the reduced atrophy evident when low levels of activity are allowed (either by partial MV support, intermittent spontaneous ventilation or bilateral electrical phrenic nerve stimulation). Even this argument does not necessarily impute inactivity as the cause of MV-induced diaphragm muscle atrophy. Within a single very active muscle like the diaphragm muscle there are differences in activity across muscle fibres of varying type (Sieck & Fournier, 1989; Sieck, 1991, 1994; Mantilla et al. 2010; Mantilla & Sieck, 2011). Muscle fibre activity within a muscle is dictated by motor unit activation: the largest muscle fibres (e.g. type IIx and IIb fibres) are typically the least active during low levels of activation (e.g. spontaneous ventilation), but the most susceptible to various conditions inducing atrophy (Sieck & Mantilla, 2013). It is likely that the low levels of activity that mitigate MV-induced diaphragm atrophy only reflect activation of a small subset of diaphragm muscle fibres. Unfortunately, the level of diaphragm activity (or inactivity) was not consistently determined in MV studies even though results have been interpreted in this context. In studies exploring ‘disuse atrophy’ of limb muscles, EMG activity persists after unloading imposed by casting, bed rest or hindlimb suspension (Blewett & Elder, 1993; Haddad et al. 2006; Roy et al. 2007). Powers et al. (2013) appear to argue that the diaphragm as a very active muscle is more susceptible to inactivity than the less active limb muscles. This argument ignores differences in basal levels of activity across diaphragm muscle fibres and certainly does not account for the greater susceptibility of type IIx and type IIb fibres to conditions inducing atrophy. Importantly, rapid muscle fibre atrophy does not occur in models where diaphragm muscle inactivity is verified (Sieck & Mantilla, 2013).
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