Blood flow-restricted exercise in space

Acute microgravity exposure results in rapid cephalad fluid shifts, space motion sickness, vestibular impairment, and musculoskeletal unloading [1]. However, the overall space environment encompasses both microgravity exposure and related challenges such as increased background radiation, social isolation, disruption of circadian rhythm (sunrise every 90 min), and access to a limited food variety (high salt prepackaged) and water supply [1]. These environmental stimuli interact to elicit chronic physiological adaptations including decreased bone mineral content and density, compromised maximal aerobic capacity, and reduced skeletal muscle mass and strength [2]. The morphological and structural alterations that occur within the skeletal muscle tissue as a result of microgravity exposure were uncovered following several Shuttle Transport System, Mir, and International Space Station (ISS) investigations [3-5]. These data suggest that the rate of skeletal muscle loss relative to the duration of microgravity exposure is nonlinear, with the greatest losses early in the mission. It is also evident that skeletal muscle atrophy and dysfunction are most prominent in the knee extensor (KE; ？6% to ？12%) and plantar flexor (PF; ？6% to ？24%) muscle groups [6].The physiological mechanisms of disuse- or unloading-related skeletal muscle atrophy have been previously reviewed [7,8]. In brief, a change in skeletal muscle size is a reflection of the temporal rates of muscle protein synthesis and degradation. For instance, across a 24-h period, if the rate of muscle protein synthesis is greater than the rate of breakdown, net muscle protein balance will be positive and protein will be gained. In contrast, if the rate of muscle protein breakdown is greater than the net rate of muscle protein synthesis, the net balance will be negative and protein will be lost. Although debated, evidence suggests that unloading induced skeletal muscle atrophy in humans occurs primarily as a result of decr