Flight Analogs Project: A Testbed for Flight Ronita L. Cromwell, Ph.D. Universities Space Research Association Flight Analogs Project Scientist NASA Johnson Space Center Overview Head Down Tilt Bed Rest History Purpose Standard conditions Standard Measures Results of Standard Measures Head Up Tilt Lunar Analog Model Current and Future Studies Testbed A testbed is a platform for experimentation for large development projects. Testbeds allow for rigorous, transparent and replicable testing of scientific theories, computational tools, and other new technologies. The term is used across many disciplines to describe a development environment that is shielded from the hazards of testing in a live or production environment. Bed Rest as a Testbed Bed rest serves as an experimental platform for rigorous examination of the physiological affects of spaceflight. Bed rest provides a controlled environment to examine countermeasures to mitigate these affects. History of Bed Rest as a Flight Analog 1961: human spaceflight begins and bed rest is used as a ground-based analog of inactivity. Early 1970s: cosmonauts return from longer duration missions difficulty sleeping due to sensation of slipping off the end of the bed Foot of the bed was raised to compensate, then gradually lowered to horizontal History of Bed Rest as a Flight Analog Soviets tested a variety of tilt angles 6º of head down tilt (HDT) optimized comfort and provided sufficient magnitude of physiological responses. HDT position provides the added benefit of studying fluid shifts 6º HDT bed rest is an accepted model for studying physiological affects of spaceflight on bone, muscle and cardiovascular systems. Purpose HDT bed rest serves as a model for studying the physiological changes that occur during spaceflight under controlled conditions; provides a platform for comparison between bed rest and space flight; provides a mechanism for testing countermeasures prior to being used in flight. NASA Flight Analogs Research Unit UTMB Children’s Hospital Flight Analogs Research Unit Standard Conditions 6º HDT bed rest Room Temperature: 70-74º Study duration ~117 days 13-15 days pre-bed rest 90 days in bed 14 days recovery Sleep/Wake cycle Wake at 0600 hrs Lights out at 2200 hrs Standard Conditions Monitored 24 hrs/day Daily Vital signs Subject monitors cameras Blood pressure Heart rate Body temperature Respiratory rate Body weight (bed scale) Fluid intake and output is measured Psychological support provided Standard Conditions Stretching twice each day Physiotherapy (massage therapy) every other day during bed rest daily for 1st week post bed rest No exercise permitted Standard Diet Isocaloric diet based on NASA spaceflight nutritional requirements Caloric intake 35.7 kcal/kg body weight (2500 calories/70 kg subject) Fluid intake 28.5 ml/kg body weight (2000 ml/70 kg subject) Carbohydrate:Fat:Protein ratio 55:30:15 No caffine, cocoa, chocolate, tea or herbal beverages All food must be consumed Caloric intake adjusted to weight within 5% Isocaloric Diet Body Mass Maintenance BW (% Δ from BR3) 7.5 C1 (n=3) C3A (n=4) C3B (n=5) 5.0 2.5 0.0 -2.5 -5.0 -7.5 -10.0 0 25 50 Day of Study 75 100 Purpose of Standard Measures Characterize human responses to head down tilt bed rest. Provide a basis for comparison between bed rest and spaceflight Provide a mechanism to assess candidate countermeasures in a multidisciplinary manner to determine outcomes on nontargeted systems. Standard Measures Neurocognitive Assessment Nutrition Pharmacokinetics WinSCAT – Psychological test of cognitive function Clinical Laboratory Assessment Blood and urine studies to monitor subject health Immune Status General immune status Viral specific immunity Latent Viral Reactivation Physiological stress Nutritional analysis Markers of bone resorption and bone formation Circulating bone and calcium regulatory factors Antioxidants and oxidative damage Lactulose/acetaminophen studies to assess gastrointestinal motility Standard Measures Bone Assessment Dual Energy X-Ray Absorptiometry (DXA) – Bone Density Peripheral Quantitative Computerized Tomography (pQCT) – lower extremity bone mass and structure Standard Measures Physical Fitness Isokinetic Testing – muscle strength/endurance Cycle Ergometry – maximum aerobic capacity Functional Fitness – strength, endurance, flexibility Standard Measures Functional Neurological Assessment Posturography testing – standing posture Stretch Reflex – monosynaptic, functional Standard Measures Cardiovascular Operational Tilt Test – orthostatic tolerance Blood volume – carbon monoxide rebreathing Echocardiography – hemodynamic assessment Results from Standard Measures Bone Consistent bone with spaceflight: loss during bed rest is most pronounced in weight bearing regions: hip, pelvis and heel. average monthly bone loss is 1-1.5% for the hip and pelvis greatest rate of bone loss occurs in the trochanter Bone biomarkers show elevated resorption with no changes in formation Sibonga, et al, ASEM in press Results from Standard Measures Cardiovascular Similar to spaceflight, plasma volume losses up to 15% occur early in bed rest (day 7). Orthostatic tolerance is reduced in bed rest, showing trends similar to spaceflight. Plasma Volume Losses during Bed Rest Plasma Volume Index (L/BSA) 1.8 1.6 1.4 * * (n=13) * 1.2 (n=3) (n=12) * * (n=6) (n=9) (n=12) (n=5) (n=7) 1.0 0.8 0 20 40 Bed Rest Day 60 80 100 Platts et al., ASEM, in press Tilt Test Survival Analyses Pre-Bed Rest Bed Rest Day 60 1.0 1.0 Survival Probability n = 9, P = 0.1 0.8 Survival Probability 0.8 0.6 0.4 0.6 0.4 Long Duration R+0 n=10 0.2 0.2 Shuttle n=44 p<0.02 0.0 0.0 0 2 4 6 Time 8 10 0 5 10 15 Time 20 25 30 Muscle Similar to spaceflight, long duration bed rest produces losses in muscle strength. Strength loss is more pronounced in the extensor (antigravity) muscles. Strength & Endurance Lee et al, ASEM, in revision Lunar Bed Rest Model As NASA prepares to return to the moon, development of a ground based lunar analog is necessary. Previous missions to the moon have not returned enough information to fully understand how the human body performs in lunar gravity. Currently there is no basis to determine if the 1/6 g lunar environment provides some degree of protection against physiological changes associated with spaceflight. Lunar Analog Feasibility Study Currently underway to assess the feasibility of using the lunar analog bed as a model for exploring the whole body physiological effects of a lunar mission. 1/6 g Bed Rest Model F = W sin (9.5deg) = 0.165 W 9.5 deg 9.5 deg W Angle required to achieve lunar gravity loads at the feet. Lunar Gravity Simulator Bed 9.5º tilt Linear bearings Counterweight system allow sled/mattress to travel on rails balance the mattress weight allowing subject to experience the true 1/6 g load Standing and seated positions permitted LAFS Protocol 11-day study 3 days pre-bed rest 6 days in bed 2 days post bed rest rehabilitation Jobst® stockings worn to simulate cardiovascular load of lunar gravity. Isocaloric Diet Feasibility determined by: Subject’s comfort assessment Foot force profiles using instrumented insoles Data comparisons against Digital Astronaut Muscle Volume Plasma Volume Urine Calcium Lunar Analog Pilot Study Successful completion of LAFS will provide the background needed to further test the platform as a long-duration model Lunar Analog Pilot Study (LAPS) – planning stages 90 days Standard conditions Standard measures Verification through Digital Astronaut until data are obtained from the lunar surface Bed Design for LAPS Adjustable Foot Support Slider Plate Assembly Floor-mounted force plate serves as a seat. Scissor jack to adjust force plate operated by subject Current Studies in HDT Gender Differences in Bed Rest: Autonomic and Neuroendocrine Changes and Vascular Response in Lower and Upper Extremities S. Platts, NASA Examination of mechanisms controlling orthostatic tolerance to determine differences between men and women Validation of Near Infrared Spectroscopy (NIRS) Measures following Bed Rest B. Soller, University Massachusetts, NSBRI, ExMC Validation of NIRS device as a noninvasive mechanism to continuously measure VO2 during exercise. Upcoming Studies in HDT Methods for the Assessment of Gastrointestinal (GI) Physiology and Function in a Reduced Gravity Analog L. Putcha, NASA Pharmacokinetics assessment of GI function using SmartPill® technology to measure pH, temperature and pressure Non-invasive Device for Measuring Core Temperature during Maximal Exercise H. Gunga, ESA, ECP Non-invasive device for estimating core temperature during maximal exercise Upcoming Studies in HDT A Quantitative Test of On-Orbit Exercise Countermeasures for Bone Demineralization Using a Bed Rest Analog P. Cavanagh, University of Washington, NASA, ECP Examination of an individualized, intermittent load replacement to protect against losses in bone mineral density, bone quality and muscle atrophy Rapid Measurements of bone loss using Tracer-less Calcium Isotope Analysis of Blood and Urine A. Anbar, Arizona State University, NASA, NxPCM Development of methods for early detection of changes in bone mineral balance through measures of calcium isotope composition in blood and urine Upcoming Studies for LAPS Determination of the Magnitude and time course of Cardiovascular Alterations during a Simulated Extended Stay Lunar Mission S. Platts, NASA Examination of the cardiovascular response to simulated lunar gravity through measures of compartmental fluid shifts, plasma volume changes and load-independent changes in cardiac function Thermoregulatory Capacity and Exercise Responses following Prolonged Lunar Analog Bed Rest D. Keller, University of Texas at Arlington, NASA, ECP Examination of thermal and cardiovascular responses to submaximal exercise Upcoming Studies for LAPS Methods for the Assessment of Gastrointestinal (GI) Physiology and Function in a Reduced Gravity Analog Validation of Near Infrared Spectroscopy (NIRS) Measures following Bed Rest B. Soller, University Massachusetts, NSBRI, ExMC Validation of NIRS device as a non-invasive mechanism to continuously measure VO2 during exercise. L. Putcha, NASA Pharmacokinetics assessment of GI function using SmartPill® technology to measure pH, temperature and pressure Flight Analogs Team J. Neigut, Project Manager J. McFather, Deputy Project Manager R. Cromwell, Project Scientist R. Buccello-Stout, Deputy Project Scientist P. Yarbough, Deputy Project Scientist S. Stranges, Bioastronautics Project Manager D. Ware, UTMB Attending Physician D. Powell, UTMB GCRC Program Director L. Wiseman, UTMB GCRC Administrator M. Ottenbacher, UTMB Head Nurse/Nurse Manager