Effect of aerobic capacity on Lower Body Negative Pressure (LBNP) tolerance in females

This investigation determined whether a relationship exists in females between: (1) aerobic capacity and Lower Body Negative Pressure (LBNP); and (2) aerobic capacity and change in LBNP tolerance induced by bed rest. Nine females, age 27-47 (34.6 plus or minus 6.0 (Mean plus or minus SD)), completed a treadmill-graded exercise test to establish aerobic capacity. A presyncopal-limited LBNP test was performed prior to and after 13 days of bed rest at a 6 deg head-down tilt. LBNP tolerance was quantified as: (1) the absolute level of negative pressure (NP) tolerated for greater than or equal to 60 sec; and (2) Luft's Cumulative Stress Index (CSI). Aerobic capacity was 33.3 plus or minus 5.0 mL/kg/min and ranged from 25.7 to 38.7. Bed rest was associated with a decrease in NP tolerance (-9.04 1.6 kPa(-67.8 plus or minus 12.0 mmHg) versus -7.7 1.1 kPa(-57.8 plus or minus 8.33 mmHg); p = 0.028) and in CSI (99.4 27.4 kPa min(745.7 plus or minus 205.4 mmHg min) versus 77.0 16.9 kPa min (577.3 plus or minus mmHg min); p = 0.008). The correlation between aerobic capacity and absolute NP or CSI pre-bed rest did not differ significantly from zero (r = -0.56, p = 0.11 for NP; and r = -0.52, p = 0.16 for CSI). Also, no significant correlation was observed between aerobic and pre- to post-rest change for absolute NP tolerance (r = -0.35, p = 0.35) or CSI (r = -0.32, p = 0.40). Therefore, a significant relationship does not exist between aerobic capacity and orthostatic function or change in orthostatic function induced by bed rest

Validation of the Pulmonary Function System for Use on the International Space Station

Aerobic deconditioning occurs during long duration space flight despite the use of exercise countermeasures (Convertino, 1996). As a part of International Space Station (ISS) medical operations, periodic tests designed to estimate aerobic capacity are performed to track changes in aerobic fitness and to determine the effectiveness of exercise countermeasures. These tests are performed prior to, during, and after missions of greater than 30 days in duration. Crewmembers selected for missions aboard the ISS perform a graded exercise test on a cycle ergometer approximately 270 days prior to their scheduled launch date in order to measure peak oxygen consumption (VO2PK) and peak heart rate (HRpk). Approximately 30 to 45 days prior to launch, crewmembers perform a submaximal cycle ergometer test at work rates set to elicit 25, 50 and 75% of their pre-flight VO2PK. This test, known as the Periodic Fitness Evaluation (PFE), serves as a baseline measure to which subsequent in-and post-flight exercise tests are compared. While onboard the ISS, crewmembers are normally scheduled to perform the PFE beginning with flight day (FD) 14 and every 30 days thereafter. The PFE is also conducted 5 and 30 days following flight. Using PFE data, aerobic fitness is estimated by quantifying the VO2 vs. HR relationship using linear regression and calculating the VO2 that would occur at the crewmember s previously measured HRpk. Currently, for data collected during flight, this technique assumes that the pre- vs. in-flight oxygen consumption per given cycle workload is similar. However, the validity of this assumption is based upon a sparse amount of data collected during the Skylab era (Michel, et al. 1977). The method of using heart rate and cycle ergometer work rates has been used to estimate aerobic fitness in normal gravity (Astrand and Ryhming, 1954; Lee, 1993). Due to spaceflight induced physiological alterations, such as shifts in extracellular fluid (e.g. plasma) volume, this method may not be valid during space flight. In addition, the ergometer onboard ISS is vibration-isolated and moves with the astronaut s application of force into the pedals. The effect of this movement on the VO2 of cycle exercise on ISS has not been quantified

Evaluation of the Danish Aerospace Corporation Portable Pulmonary Function System

A research project designed to investigate changes in maximal oxygen consumption (VO2max) during and following long duration flight on the International Space Station (ISS) has recently been completed. The device used to measure VO2 on board ISS, the Portable Pulmonary Function System (PPFS) manufactured by the Danish Aerospace Corporation (DAC), is based on previous-generation devices manufactured by DAC, but the PPFS has not been validated for analyzing metabolic gases or measuring cardiac output (Qc). The purpose of the present evaluation is to compare PPFS metabolic gas analysis measurements to measurements obtained using a clinically-validated system (ParvoMedics TrueOne(c) 2400 system; Parvo). In addition, Qc data collected with the PPFS were compared to Qc measurements from echocardiography. METHODS: Ten subjects completed three cycle exercise tests to maximal exertion. The first test was conducted to determine each subject's VO2max and set the work rates for the second and third (comparison) tests. The protocol for the two comparison tests consisted of three 5-minute stages designed to elicit 25%, 50%, and 75% VO2max (based upon results from the initial test), followed by 1-minute stages of increasing work rate (25 watt/minute) until the subject reached maximal effort. During one of the two comparison tests, metabolic gases and Qc were assessed with the PPFS; metabolic gases and Qc were assessed with the Parvo and by echocardiography, respectively, during the other test. The order of the comparison tests was counterbalanced. VO2max and maximal work rate during the comparison tests were compared using t tests. Mixed-effects regression modeling was used to analyze submaximal data. RESULTS: All of the data were within normal physiological ranges. The PPFS-measured values for VO2max were 6% lower than values obtained with the Parvo (PPFS: 3.11 +/- 0.75 L/min; Parvo: 3.32 +/- 0.87 L/min; mean +/- standard deviation; P = 0.02); this difference is probably due to flow restriction imposed by the PPFS Qc accessories. Submaximal VO2 values were slightly lower when measured with the PPFS, although differences were not physiologically relevant. The PPFS-measured values of submaximal carbon dioxide production (VCO2) were lower than the data obtained from Parvo, which could be attributed to lower fractions of expired carbon dioxide measured by the PPFS. The PPFS Qc values tended to be lower than echocardiography-derived values. CONCLUSIONS: The results of the present study indicate a need to further examine the PPFS and to better quantify its reproducibility; however, none of the findings of the current evaluation indicate that the PPFS needs to be replaced or modified

Reliability of the Danish Aerospace Corporation Portable Pulmonary Function System

Metabolic gas analysis is a critical component of investigations that measure cardio-pulmonary exercise responses during and after long-duration spaceflight. The primary purpose of the current study was to determine the reliability and intra-subject repeatability of a metabolic gas analysis device, the Portable Pulmonary Function System (PPFS), designed for use on the International Space Station (ISS). The second objective of this study was to directly compare PPFS measurements of expired oxygen and carbon dioxide (FEO2 and FECO2) to values obtained from a well-validated clinical metabolic gas analysis system (ParvoMedics TrueOne (c) [PM]). Eight subjects performed four peak cycle tests to maximal exertion. The first test was used to prescribe work rates for the subsequent test sessions. Metabolic gas analysis for this test was performed by the PM, but samples of FEO2 and FECO2 also were simultaneously collected for analysis by the PPFS. Subjects then performed three additional peak cycle tests, consisting of three 5-min stages designed to elicit 25%, 50%, and 75% maximal oxygen consumption (VO2max) followed by stepwise increases of 25 W/min until subjects reached volitional exhaustion. Metabolic gas analysis was performed using the PPFS for these tests. Intraclass correlation coefficients (ICC), within-subject standard deviations (WS SD), and coefficients of variation (CV%) were calculated for the repeated exercise tests. Mixed model regression analysis was used to compare paired FEO2 and FECO2 values obtained from the PPFS and the PM during the initial test. The ICC values for oxygen consumption (VO2), carbon dioxide production (VCO2), and ventilation (VE) indicate that the PPFS is highly reliable (0.79 to 0.99) for all exercise levels tested; however, ICCs for respiratory exchange ratio (RER) were low ( 0.11 - 0.51), indicating poor agreement between trials during submaximal and maximal exercise. Overall, CVs ranged from 1.6% to 6.7% for all measurements, a finding consistent with reported values that were obtained using other metabolic gas analysis techniques. The PPFS and PM produced comparable FEO2 data; however, there was less agreement between measures of FECO2 obtained from the two devices, particularly at lower CO2 concentrations. The PPFS appears, in practically all respects, to yield highly reliable metabolic gas analysis data. Lower reliability of RER measurements reported in the literature and likely is not a function of the PPFS device. Further examination of PPFS CO2 data is warranted to better understand the limitations of these PPFS measurements. Overall, the PPFS when used for repeated measures of cardio-pulmonary exercise should provide accurate and reliable data for studies of human adaptation to spaceflight

Peak Oxygen Uptake during and after Long-duration Space Flight

Aerobic capacity (VO2peak) previously has not been measured during or after long-duration spaceflight. PURPOSE: To measure VO2peak and submaximal exercise responses during and after International Space Station (ISS) missions. METHODS: Astronauts (9 M, 5 F: 49 +/- 5 yr, 175 +/- 7 cm, 77.2 +/- 15.1 kg, 40.6 +/- 6.4 mL/kg/min [mean +/-SD]) performed graded peak cycle tests ~90 days before spaceflight, 15 d (FD15) after launch and every ~30 d thereafter during flight, and 1 (R+1), 10 (R+10), and 30 d (R+30) after landing. Oxygen consumption (VO2) and heart rate (HR) were measured from rest to peak exercise, while cardiac output (Q), stroke volume (SV), and arterial-venous oxygen difference (a-vO2diff) were measured only during rest and submaximal exercise. Data were analyzed using mixed-model linear regression. Body mass contributed significantly to statistical models, and thus results are reported as modeled estimates for an average subject. RESULTS: Early inflight (FD15) VO2peak was 17% lower (95% CI = - 22%, -13%) than preflight. VO2peak increased during spaceflight (0.001 L/min/d, P = 0.02) but did not return to preflight levels. On R+1 VO2peak was 15% (95% CI = -19%, -10%) lower than preflight but recovered to within 2% of preflight by R+30 (95% CI = -6%, +3%). Peak HR was not significantly different from preflight at any time. Inflight submaximal VO2 and a-vO2diff were generally lower than preflight, but the Q vs. VO2 slope was unchanged. In contrast, the SV vs. VO2 slope was lower (P < 0.001), primarily due to elevated SV at rest, and the HR vs. VO2 slope was greater (P < 0.001), largely due to elevated HR during more intense exercise. On R+1 although the relationships between VO2 and Q, SV, and HR were not statistically different than preflight, resting and submaximal exercise SV was lower (P < 0.001), resting and submaximal exercise HR was higher (P < 0.002), and a-vO2diff was unchanged. HR and SV returned to preflight levels by R+30. CONCLUSION: In the average astronaut VO2peak was reduced during spaceflight and immediately after landing but factors contributing to lower VO2peak may be different during spaceflight and recovery. Maintaining Q while VO2 is reduced inflight may be suggestive of an elevated blood flow to vascular beds other than exercising muscles, but decreased SV after flight likely reduces Q at peak exertion

Oxygen Uptake Responses to Submaximal Exercise Loads Do Not Change During Long-Duration Space Flight

In previous publications we have reported that the heart rate (HR) responses to graded submaximal exercise tests are elevated during long-duration International Space Station (ISS) flights. Furthermore, the elevation in HR appears greater earlier, rather than later, during the missions. A potential confounder in the interpretation of HR results from graded exercise tests on ISS is that the cycle ergometer used (CEVIS) is vibration-isolated from the station structure. This feature causes the CEVIS assembly to sway slightly during its use and debriefing comments by some crewmembers indicate that there is a "learning curve" associated with CEVIS use. Therefore, one could not exclude the possibility that the elevated HRs experienced in the early stages of ISS missions were related to a lowered metabolic efficiency of CEVIS exercise that would raise the submaximal oxygen uptake (VO2) associated with graded exercise testing work rates

Exercise Countermeasures Demonstration Project During the Lunar-Mars Life Support Test Project Phase 2A

This demonstration project assessed the crew members' compliance to a portion of the exercise countermeasures planned for use onboard the International Space Station (ISS) and the outcomes of their performing these countermeasures. Although these countermeasures have been used separately in other projects and investigations, this was the first time they'd been used together for an extended period (60 days) in an investigation of this nature. Crew members exercised every day for six days, alternating every other day between aerobic and resistive exercise, and rested on the seventh day. On the aerobic exercise days, subjects exercised on an electronically braked cycle ergometer using a protocol that has been previously shown to maintain aerobic capacity in subjects exposed to a space flight analogue. On the resistive exercise days, crew members performed five major multijoint resistive exercises in a concentric mode, targeting those muscle groups and bones we believe are most severely affected by space flight. The subjects favorably tolerated both exercise protocols, with a 98% compliance to aerobic exercise prescription and a 91% adherence to the resistive exercise protocol. After 60 days, the crew members improved their peak aerobic capacity by an average 7%, and strength gains were noted in all subjects. These results suggest that these exercise protocols can be performed during ISS, lunar, and Mars missions, although we anticipate more frequent bouts with both protocols for long-duration spaceflight. Future projects should investigate the impact of increased exercise duration and frequency on subject compliance, and the efficacy of such exercise prescriptions

Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome

SCYX-7158, an oxaborole, is currently in Phase I clinical trials for the treatment of human African trypanosomiasis. Here we investigate possible modes of action against Trypanosoma brucei using orthogonal chemo-proteomic and genomic approaches. SILAC-based proteomic studies using an oxaborole analogue immobilised onto a resin was used either in competition with a soluble oxaborole or an immobilised inactive control to identify thirteen proteins common to both strategies. Cell-cycle analysis of cells incubated with sub-lethal concentrations of an oxaborole identified a subtle but significant accumulation of G2 and >G2 cells. Given the possibility of compromised DNA fidelity, we investigated long-term exposure of T. brucei to oxaboroles by generating resistant cell lines in vitro. Resistance proved more difficult to generate than for drugs currently used in the field, and in one of our three cell lines was unstable. Whole-genome sequencing of the resistant cell lines revealed single nucleotide polymorphisms in 66 genes and several large-scale genomic aberrations. The absence of a simple consistent mechanism among resistant cell lines and the diverse list of binding partners from the proteomic studies suggest a degree of polypharmacology that should reduce the risk of resistance to this compound class emerging in the field. The combined genetic and chemical biology approaches have provided lists of candidates to be investigated for more detailed information on the mode of action of this promising new drug clas

Formation of metre-scale bladed roughness on Europa's surface by ablation of ice

On Earth, the sublimation of massive ice deposits at equatorial latitudes under cold and dry conditions in the absence of any liquid melt leads to the formation of spiked and bladed textures eroded into the surface of the ice. These sublimation-sculpted blades are known as penitentes. For this process to take place on another planet, the ice must be sufficiently volatile to sublimate under surface conditions and diffusive processes that act to smooth the topography must operate more slowly. Here we calculate sublimation rates of water ice across the surface of Jupiter’s moon Europa. We find that surface sublimation rates exceed those of erosion by space weathering processes in Europa’s equatorial belt (latitudes below 23°), and that conditions would favour penitente growth. We estimate that penitentes on Europa could reach 15 m in depth with a spacing of 7.5 m near the equator, on average, if they were to have developed across the interval permitted by Europa’s mean surface age. Although available images of Europa have insufficient resolution to detect surface roughness at the multi-metre scale, radar and thermal data are consistent with our interpretation. We suggest that penitentes could pose a hazard to a future lander on Europa