Phase I -ground based integrated strength & cardiovascular (CV) exercise training under normal weight bearing conditions.

Phases 2&3 - application of this protocol with progressive levels of inactivity.

Measurements - total body physical work capacity, muscular mass, strength, and sustained muscle endurance (i.e., extravehicular activity, EVA, related issues). CV-related exercise using M-MED "aerobic" mode configuration designed to minimize the time spent in exercise using high power output, short duration interval training. On alternate days, the M-MED will be configured for strength training which has been shown to result in increased muscle strength and size. These studies will validate the efficacy of concurrent endurance and strength training as a high economy approach to flight crew physical fitness, using a scientifically proven exercise modality that has a high probability for use during prolonged space flight missions. This work directly addresses primary requirements in the National Space Biomedical Research Institute (NSBRI) Request for Applications (RFA):

1. "New, innovative exercise hardware for deployment on CEV and Martian surfaces that provide efficient means for maintenance of aerobic capacity, bone and muscle strength, and endurance with sufficient reserve for contingencies."

2. "New, innovative exercise protocols that minimize in-flight crew time necessary to maintain aerobic capacity and muscle strength and endurance, and facilitate reserve for contingencies on lunar and Martian missions."

Electromyography (EMG) studies demonstrate that similar activation levels are seem in key muscles during either M-MED based or free weight resistance exercise. EMG during rowing demonstrate that the thigh, leg, and arm muscles are robustly activated. Endurance mode exercise was also found to stimulate recruitment of the muscles which support the spine. In a recently completed study, 32 subjects (16 male, 16 female) completed 5 weeks of combined resistance and endurance training using the M-MED. Muscle strength increased ~20% while aerobic fitness measured as maximal oxygen consumption (VO2max) increased ~8%. M-MED training increased time to hand grip fatigue by ~70% and leg extension fatigue by ~27%. Thigh muscle cross sectional area increased ~11% as a result of training. Additional deliverables include cross validation of VO2max testing results between the M-MED device and laboratory standard cycle ergometry based testing protocols. As requested by NASA, additional studies have demonstrated that M-MED based exercise can increase the size and strength of the calf and hamstrings muscle groups. These results demonstrate that the M-MED device can be used for both training and physical work capacity testing providing a platform for in-flight assessment.

In summary, findings to date indicate that the gravity independent M-MED is a viable option for resistance- and endurance-mode exercise during flight and/or planetary exploration thereby addressing two critical risks: 1) Cardiovascular deconditioning; 2) Decreased muscle strength, endurance, and size (atrophy). Endurance mode exercise may have the added benefit of maintaining and, possibly, improving endurance of arm muscles of flight crews as well as aiding in the maintenance of lower back stability and loading during flight and planetary exploration.

Presentations at workshops and meetings are listed below and also in the Bibliography section:

Countermeasure Exercise Using a Single, Gravity Independent, Device to Prevent Cardiovascular and Muscular Deconditioning. J. Cotter, T. Owerkowicz, F. Haddad, P. Tesch, V. Caiozzo, G. Adams. American Society for Gravitational and Space Biology Annual Meeting, 2011.

Resistance and aerobic flywheel training improves muscle strength and aerobic capacity in ambulatory subjects. Owerkowicz T, Cotter JA, Yu AM, Camilon ML, Hoang T, Baker MJ, Pandorf C, Kreitenberg A, Baldwin KM, Tesch PA, Caiozzo VJ, Adams GR. 18th Humans in Space symposium of the International Academy of Astronauts. Houston, TX, 2011.

Gravity-independent flywheel exercise training improves aerobic capacity and muscle strength in ambulatory subjects. Owerkowicz T, Cotter JA, Tesch PA, Caiozzo VJ, Adams GR. Experimental Biology Washington, DC, 2011

DNA Methylation is Altered in Human Skeletal Muscle in Response to Exercise Training. Shlomit Radom-Aizik, Fadia Haddad, Tomasz Owerkowicz, Joseph M. Devaney, Eric P. Hoffman, Per A. Tesch, Gregory R. Adams. American College of Sports Medicine Annual Meeting, 2012

Influence of 10 days of unilateral lower limb suspension and combined exercise training on human vastus lateralis and soleus muscles. J. Cotter, F. Hadad, A. Yu, T. Hoang, M. Baker, P. Tesch, K. Baldwin, V. Caiozzo, G. Adams. Experimental Biology Annual Meeting, 2012.

The presence and regulation of antisense long non-coding RNA with altered myosin expression in exercising human muscle. Clay E. Pandorf, Fadia Haddad, Tomasz Owerkowicz, Kenneth M. Baldwin, Vincent J. Caiozzo, Gregory R. Adams. Experimental Biology, 2012.

The Effects Of Muscle Unloading With And Without Exercise Countermeasures On Loading Sensitive Cellular And Molecular Biomarkers. G. Adams, J. Cotter, C. Pandorf, F. Haddad, P. Tesch, K. Baldwin,V. Caiozzo. NASA Human Research Program (HRP) Meeting, 2012.

Counteracting decrements in muscle function and aerobic capacity during unloading utilizing a gravity independent device. Cotter J, Hoang T, Yu A, Tesch P, Caiozzo V, Adams G. Podium presentation at the Annual Meeting for the American College of Sports Medicine, San Francisco, CA, 2012.

1. "New, innovative exercise hardware for deployment on CEV and Martian surfaces that provide efficient means for maintenance of aerobic capacity, bone and muscle strength, and endurance with sufficient reserve for contingencies".

2. "New, innovative exercise protocols that minimize in-flight crew time necessary to maintain aerobic capacity and muscle strength and endurance, and facilitate reserve for contingencies on lunar and Martian missions".

1. "New, innovative exercise hardware for deployment on CEV, lunar and Martian surfaces that provide efficient means for maintenance of aerobic capacity, bone and muscle strength, and endurance with sufficient reserve for contingencies".

2. "New, innovative exercise protocols that minimize in-flight crew time necessary to maintain aerobic capacity and muscle strength and endurance, and facilitate reserve for contingencies on lunar and Martian missions".

Year 2 training studies involve eight weeks of subject participation and are conducted in serial campaigns. To date, three eight week campaigns have been completed. A total of sixteen subjects have completed training. In addition, nine subjects are currently participating in campaign number four. Data analysis is ongoing. Interim results indicate that subjects completing the combined interval endurance plus heavy resistance training protocol experienced significant increases in: VO2 max (12%), 3RM (18%) and myofiber cross sectional area (14.5%). These results indicate that training on the M-MED device has the potential to address two critical risks: 1) cardiovascular deconditioning; 2) Decreased muscle strength and size (atrophy). Additional deliverables from year 2 include cross validation of VO2 testing results between the M-MED device and laboratory standard cycle ergometry based testing protocols (r=0.95, p<0.0001; n=16). These results indicate that the M-MED device can be used for both training and physical work capacity testing providing a platform for in-flight assessment.

This work directly addresses primary requirements in the NSBRI RFA:

1. "New, innovative exercise hardware for deployment on CEV, lunar and Martian surfaces that provide efficient means for maintenance of aerobic capacity, bone and muscle strength, and endurance with sufficient reserve for contingencies".

2. "New, innovative exercise protocols that minimize in-flight crew time necessary to maintain aerobic capacity and muscle strength and endurance, and facilitate reserve for contingencies on lunar and Martian missions".

The M-MED device itself represents a potentially useful modality for the maintenance of both cardiovascular and musculoskeletal health. This could be of benefit in circumstances when limitations in cost or space requirements preclude the availability of a wide spectrum of exercise equipment.

As presented at the recent NASA HRP workshop, preliminary studies using the M-MED device indicate that foot force measurements of resistance mode exercise are similar to those seen using free weight exercises. Similarly, electromyography (EMG) studies demonstrate that similar activation levels are seem in key agonist muscles during either M-MED based or free weight resistance exercise. These findings indicate that the gravity independent M-MED is a viable option for resistance mode exercise during flight and during planetary exploration.

When configured for endurance mode rowing exercise, EMG measurements indicate that, in addition to the thigh and leg muscles, there is a robust activation of upper and forearm muscles. This suggests that M-MED endurance mode exercise may have the added benefit of maintaining and, possibly, improving strength and endurance of arm muscles of flight crews.

Significantly, endurance mode exercise also stimulated robust recruitment of the muscles which support the spine. This finding suggests that M-MED based exercise may promote the maintenance of lower back stability and loading during flight and planetary exploration.

Foot force measurements obtained during endurance mode rowing exercise demonstrated that forces equivalent to earth normal walking (e.g., 1G) were generated during this exercise. This result indicates that, in addition to the cardiovascular benefits of this exercise, time spent rowing will contribute to musculoskeletal loading as well. This suggests that M-MED endurance mode exercise should contribute significantly to crew health maintenance while maximizing the value of time spent on countermeasure exercise.

In response to NASA JSC requests, the M-MED device has been instrumented to provide power output measurements during endurance mode exercise. This technological modification will facilitate the monitoring of crew exercise volume. The addition of this capability will also allow the M-MED device to be used for in-flight and planetary quantitative exercise capacity testing of crew members.

Phase I -ground based integrated strength & CV exercise training under normal weight bearing conditions.

Phases 2&3 - application of this protocol with progressive levels of inactivity. Measurements - total body physical work capacity, muscular mass, strength and sustained muscle endurance (i.e., EVA related issues). CV-related exercise using M-MED "aerobic" mode configuration designed to minimize the time spent in exercise using high power output, short duration interval training. On alternate days, the M-MED will be configured for strength training which has been shown to result in increased muscle strength and size.

These studies will validate the efficacy of concurrent endurance and strength training as a high economy approach to flight crew physical fitness, using a scientifically proven exercise modality that has a high probability for use during prolonged spaceflight missions. This work directly addresses primary requirements in the NSBRI RFA:

1. "New, innovative exercise hardware for deployment on CEV, lunar and Martian surfaces that provide efficient means for maintenance of aerobic capacity, bone and muscle strength, and endurance with sufficient reserve for contingencies".

2. "New, innovative exercise protocols that minimize in-flight crew time necessary to maintain aerobic capacity and muscle strength and endurance, and facilitate reserve for contingencies on lunar and Martian missions".