The Tumor Microenvironment: The Making of a Paradigm

What has been will be again, what has been done will be done again; there is nothing new under the su

Adaptive conditioning of skeletal muscle in a large animal model (Sus domesticus)

Recognition of the adaptive capacity of mammalian skeletal muscle has opened the way to a number of clinical applications. For most of these, the fast, fatigue-susceptible fibres need to be transformed stably to fast, fatigue-resistant fibres that express the 2A myosin heavy chain isoform. The thresholds for activity-induced change are size-dependent, so although the requisite patterns of electrical stimulation are known for the rabbit, in humans these same patterns would produce type 1 fibre characteristics, with an undesirable loss of contractile speed and power. We have used histochemistry, immunohistochemistry and electrophoretic separations to evaluate a possible conditioning regime in a large animal model. Stimulation of the porcine latissimus dorsi muscle with a phasic 30-Hz pattern for up to 41 days converted all type 2X and 2A/2X fibres to 2A with only a small increase in the type 1 population, from 17% to 22%. Stimulation for longer periods increased the proportion of type 1 fibres to 52%. Based on this model, stimulation regimes designed to achieve a stable 2A phenotype in humans should deliver fewer stimulating impulses, possibly by a factor of 2, than the pattern assessed here. Any such pattern needs to be tested for at least 8 weeks