The Effects of Whole Body Unloading on Physiological Function

Overview

This study is a collaboration between the Centre of Human \& Aerospace Physiological Sciences (CHAPS) and the Sleep and Brain Plasticity Centre (Department of Neuroimaging) at King's College London and the Sleep Disorders Centre at Guy's Hospital.The main purpose of the study is to evaluate the effects of a 7 day unloading period (simulating micro gravity) on muscle mass using three independent methods; two scanning techniques (magnetic resonance imaging (MRI) and dual x-ray absorptiometry (DXA)) and one that involves swallowing a capsule that contains a harmless chemical called creatine (D3-Creatine (D3-cr)) and then measuring its concentration in urine. In order to induce muscle loss, participants will be required to lie flat on their back on a water bed filled with water and salt (called hyper-buoyancy flotation (HBF)). As this situation is similar to that experienced in space, the investigators will also measure the effect of HBF on sleep, brain and physiological function - all things known to change in astronauts. Sixteen male subjects (18-40 yrs) will be recruited to participate in the study that will require physiological testing before, during and following both 7 days of normal conditions and 7 days of HBF bed-rest. Each subject will be exposed to the same conditions and assessments over the study period. As some loss of muscle is expected, participants will be offered an exercise rehabilitation programme upon completion of HBF with self-monitored and/or guided sessions based on those provided by the Space Medicine Office of the European Space Agency to returning astronauts.

The rapid loss of skeletal muscle occurs in extreme physiological conditions, most notably within intensive care, hypoxia and during spaceflight. The cause of this accelerated loss is unknown; however, interventions aiming to slow the decline may have profound effects on quality of life post-surgery and, in space expedition terms, the ability to complete mission critical tasks. In addition, the current methodologies available to measure total skeletal muscle mass have limitations, lack accuracy (anthropometry and Bioelectrical Impedance Analysis (BIA)) or are immobile and costly (dual x-ray absorptiometry (DXA) and magnetic resonance imaging (MRI)). The primary aim of this study is to investigate whole body skeletal muscle loss induced through 7 consecutive days of whole-body immobilisation using three independent methods; dual x-ray absorptiometry (DXA), magnetic resonance imaging (MRI) and D3-Creatine dilution (D3-cr). A number of secondary aims are also targeted, which have the shared objective to measure the impact of 7-days of immobilisation on HBF; 1. Muscular, neuromuscular and cardiovascular adaptation; 2. Neurophysiology, sleep architecture and cognition; 3. A range of spaceflight specific measures, aiming to characterise the intervention proposed within this study (hyper-buoyancy flotation (HBF) bed rest) as an alternative ground-based analogue to observe the physiological response to microgravity. The muscular, neuromuscular and cardiovascular research is performed by King's College London Centre of Human \& Aerospace Physiological Sciences (KCL CHAPs) and ranges from measurement of whole-body change, to cellular adaptation. Total skeletal muscle mass will be measured using DXA, MRI and D3-cr as well as the cross-sectional area of a single muscle group (quadriceps) using ultrasound. A biopsy will be taken from the same muscle group (quadriceps) in order to investigate changes in muscle protein synthesis (MPS), myofibre size, force and protein: DNA ratio. Muscle performance will also be measured, from whole-body power output using a countermovement jump, to force expressed by the trunk, quadriceps, calf and handgrip. Muscle tone will be measured in three flexor and three extensor muscles in the calf, forearm and lower back. The plantarflexion muscles in the calf will be further assessed, with ankle proprioception, maximal strength and surface EMG of the medial gastrocnemius measured. Blood samples will be taken in order to distinguish changes in immunity and bone markers. The subject's height will be measured and intervertebral disc morphology distinguished using ultrasound and MRI. The neuromuscular and muscle performance measurements will be obtained concurrently. Electrical activity produced by the skeletal muscles will be recorded and evaluated using electromyography (EMG). Prior to the force expression of the quadriceps being tested, pads will also be positioned for the muscle to be electrically stimulated and for a maximal involuntary force to be measured. Lastly, a cycle ergometer assessment will be undertaken, where power is ramped gradually and maximal aerobic utilisation (VO2max) determined. The neurophysiology, sleep architecture and cognition investigation will be in collaboration with the Sleep and Brain Plasticity Centre (Department of Neuroimaging, IoPPN) and the Sleep Disorders Centre at Guy's Hospital. This study will look at any ensuing changes in sleep architecture and neurophysiology. Any associated cognitive or brain structural changes, which may be induced through 1 week of whole-body immobilisation, will also be investigated. The procedures outlined are designed to assess known physiological adaptations occurring as a consequence of a micro-gravity environment, and therefore prove useful comparative tools from which the HBF model can be evaluated. Sixteen male subjects (18-40 yrs) will be recruited to undertake test procedures pre- and post- a 7-day control period, where they will continue their habitual activities and be provided with their total (controlled) calorie intake, and pre- and post- a 7-day unloading period, where subjects will be required to remain on a hyper-buoyancy flotation (HBF) bed.