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We hypothesized that supine LBNP treadmill exercise combined with Flywheel resistive exercise maintains upright physiologic responses following 60-days of head-down tilt (HDT) bed rest (BR). METHODS: 16 healthy women (age 25-40 years) underwent 60-days HDT (-6deg.) BR. Women were assigned to either a non-exercise control group (CON, n=8) or to an exercise group (EX, n=8). EX subjects performed a 40-min, variable intensity LBNP exercise protocol at foot-ward forces between 1.0-1.1 times body weight, followed by 10- min of resting LBNP 3-4 days/week. Resistive exercise of maximal concentric and eccentric supine leg press and heel raise exercises were performed using a flywheel ergometer 2-3 days/week. IRBs approved this study with informed/written consent. RESULTS: Post-BR VO2pk was not different in EX (-3.3+/-1.2%) but decreased significantly in CON (-21.2+/-2.1%), p< 0.05. Post-BR orthostatic tolerance time (mean se) decreased significantly less in EX (19.3+/-1.3 to 14.4+/-1.5 min) than in CON (17.5+/-0.1 to 9.1+/- 1.5 min), p=0.03. Post-BR muscle strength decreased significantly in CON, but was preserved in EX. Post-BR bone resorption was greater than pre-BR in both groups (p<0.05). Bone formation markers, were significantly elevated (p<0.05) in EX than in CON. CONCLUSIONS: Supine LBNP treadmill exercise along with flywheel resistive exercise maintains upright exercise capacity, orthostatic responses and muscle strength during 60-days HDT BR.

Sixteen women who participated in the WISE-2005 headdown bed rest (HDBR) were studied before and on day 56 of bed rest to test the hypothesis that chronic changes in circulating norepinephrine (NOR) would change the response to adrenergic receptor agonists. Five minute infusions of 2 doses of isoproterenol (ISO), and 2 doses of NOR were administered while heart rate (HR), mean arterial pressure (MAP) and total peripheral resistance (TPR) were measured. Before HDBR, the higher dose of ISO increased HR by 13 beats/min (P

Sixteen women were studied before, during and after a 60 day, continu ous 6" head-down bed-rest (HDBR). Subjects were randomly assigned to two groups: Control (no countermeasures) and Exercise+LBNP (supine ru nning within an LBNP chamber for 40-min followed by 10-min passive L BNP for 3-4 days/week, plus flywheel resistive training of the legs e very third day). Cardiovascular responses were observed before bed re st, on day 50 of HDBR and R+8 after bed rest. Subjects were supine in the LBNP device with suction applied at 0, -10, -20 and -30 mmHg LBN P for 2-min per stage. In the pre-bed rest testing, there was no diff erence in HR between the groups at rest or at -30 mmHg. On HDBR day 50, HR was elevated at supine rest for the Con not the Ex group, whil e at -30 mmHg HR was elevated above pre-HDBR for both groups, but the magnitude of increase from Pre- to HDBR day 50 was less for the Ex g roup than for the Con group. The change in HR on HDBR day 50 is an im portant indicator as it was less than 24-hours after the Exercise+LBN P countermeasure on day 49. After bed rest, no specific countermeasu res were provided in the first week, so HR responses on day R+8 refle cted the effects of bed rest with or without countermeasure plus any recovery from simply returning to the upright posture. Relative to th e Pre-bed rest responses, HR on day R+8 had recovered in the Ex group but was still elevated in the Con group. These results indicate that the cardiovascular response to LBNP is preserved to a greater degre e during bed rest by the countermeasures, and further that the cardio vascular response returned to pre-bed rest much more rapidly in the E xercise+LBNP group than hi the group that received no cardiovascular countermeasures.

During 2005, 24 women will take part in the Women International Space-simulation for Exploration (WISE). In this paper we report on the first phase that studied 4 Exercise (EX+LBNP), 4 nutrition (NUT), and 4 no countermeasure control (CON) subjects. The EX+LBNP group completed regular exercise on a treadmill inside LBNP, flywheel resistive exercise and static periods of LBNP, and had recovery days. The NUT group received daily protein supplements. Integrative cardiovascular responses were obtained and here we report data for heart rate during LBNP, blood volume and angiotensin 11. LBNP was applied at 0, -10, -20 and -30 mmHg for 2-minutes for each stage. Blood was sampled prebed rest and on HDT-60. After 60-days head down bed rest, HR in the CON group increased by 6.1+/-2.8 bpm at rest and by 20.7+/-5.0 bpm at -30 mmHg LBNP. The EX+LBNP group had increases of 3.6+/-5.6 and 11.6+/-5.4 bpm, while the NUT group HR increased 2.6+/-3.1 and 9.4+/-3.6 bpm. The EX+LBNP group had almost no change in blood volume or plasma angiotensin II from pre-bed rest to HDT60, while both the CON and NUT groups had larger increases in plasma volume and almost double concentrations of angiotensin II. These data show a positive effect in the EX+LBNP group on the heart rate response as well as an unexpected possible benefit in the NUT group. Further studies are required to confirm possible cardiovascular benefits of the protein supplement.

Previous exercise in space has lacked sufficient loads to maintain preflight cardiovascular and musculoskeletal mass and function. Lower body negative pressure (LBNP) produces a static force equivalent to one Earth body weight by each 52 mm Hg of LBNP during supine posture. LBNP also provides transmural blood pressures simulating upright exercise. Thus, this artificial-gravity concept may help maintain cardiovascular and musculoskeletal systems of crewmembers during prolonged exposure to microgravity. Currently available, bungee cord assisted, treadmill exercise is limited by harness discomfort, lower than normal loads, abnormal post-flight gait, and the absence of gravitational blood pressures within the vascular system. PURPOSE: This project evaluates a method to create artificial gravity using supine LBNP treadmill exercise to prevent loss of physiologic function in microgravity simulated by 30 days of bed rest. Identical twins were used as volunteers so that statistical power could be maximized. This countermeasure is being transitioned to space flight. CURRENT STATUS OF RESEARCH Methods: Six sets of identical twins (6 females and 14 males, 21-36 years) remained in 6 head-down tilt (HDT) bed rest for 30 days to simulate prolonged microgravity. Six subjects were randomly selected to exercise supine in an LBNP chamber for 40 minutes six days per week (EX group), while their twin brothers served as non-exercise controls (CON). Pressure within the exercise LBNP chamber was adjusted to increase load, hence increasing exercise intensity. During supine treadmill exercise, LBNP (52-63 mmHg) was applied to produce foot ward forces equivalent to those for upright running on Earth at 1.0-1.2 times body weight (BW) and subjects performed an interval exercise protocol (40-80% peak exercise capacity [VO2pk]). Five minutes of resting LBNP immediately followed each exercise session. Results: Orthostatic tolerance time decreased significantly after 30 days bed rest in the CON group, but was relatively maintained in the EX group. VO2pk was maintained in EX males, but not in CON males. Isokinetic knee strength (extension, peak torque) decreased significantly in CON males, but was preserved in EX males. The EX group had significantly higher spine muscle strength after bed rest than the CON group. The cross-sectional area of spinal muscle at L4/5 level decreased significantly in the CON group but not in the EX group. Urinary n-telopeptide excretion, an index of bone resorption, was increased during bed rest in CON, but not in EX subjects. This suggests protection by LBNP exercise against the increase in bone resorption typically seen in simulated and actual microgravity. Significant changes in bone mineral density (BMD) in the spine and ribs were observed in CON subjects, but not in EX subjects. Conclusions: Our treadmill exercise protocol within LBNP plus a short period of post-exercise LBNP maintains orthostatic responses, upright exercise capacity and other important physiologic parameters during bed rest. These results document the efficacy of our apparatus and exercise protocol for maintaining physiologic structure and function during long-duration microgravity as simulated by 30 days of HDT bed rest. FUTURE PLANS: More sets of female identical twins are needed to reach significance. The LBNP exercise chamber will be redesigned for flight.