is a reflection of diminished venous return and contracted effective circulating blood volume induced by spaceflight factors. skeletal muscle atrophy is mentioned with respect to its possible contribution to exercise intolerance, and in some of the later apollo flights lower limb girth measurements were completed (data not published) that provided the first evidence for loss of muscle mass in the legs. skylab the skylab program (may 1973 – november 1974) was from the onset, intended to provide a life sciences laboratory in space. a significant number of experiments were conducted to provide physiologic data from humans exposed to long-duration stays in a microgravity environment. a 56-day ground-based simulation of many of the skylab experiments, conducted in an environmentally-controlled, enclosed chamber, was termed the skylab medical experiments altitude test and represented the first mission. the three subsequent orbital missions were termed skylab 2, 3 and 4. these three long-duration mission were 28, 56 and 84 days in duration, respectively. collectively, the skylab missions achieved a milestone in providing a vast array of human spaceflight biomedical information during missions of longer duration than any previous mission. with respect to the current issue of loss of muscle mass and function, two key studies were performed during the course of the three skylab orbital missions. first, leg and arm volumes were calculated by measuring the girth (circumference) of contiguous 3-centimeter arm and leg segments, treating all the segments as a short tapered cylinder, and then summing the segment volumes to obtain the volume of each extremity. the second study included the first muscle strength measurements by means of a dynamometer. in addition to measurements relating directly to skeletal muscle strength and mass, indirect measurements were made that demonstrated that all skylab crewmembers had a negative nitrogen balance indicative of skeletal muscle attrition. this was also observed 10 years later in short-duration space shuttle crewmembers. figure 6-2. changes in upper and lower limb volumes obtained by circumference measurements of 3-cm segments in the three crewmembers from skylab 4. because of a much higher exercise volume in the skylab 4 crewmembers, their loss of muscle volume was much less than observed in crewmembers from skylab 2 and 3. from reference. upper and lower limb volumes obtained on the three crewmembers of skylab 4 are shown in figure 6-2. fluid shifts contributed the largest changes to lower limb volumes, but loss of leg tissue mass is clearly evident, particularly in the commander. as shown in the graphs, significant loss of leg volume occurs within the first few days of microgravity exposure while changes in the upper limbs are less remarkable. upon return to earth, much of the loss of leg volume is corrected and there is often a short over-correction or overshoot. once this fluid shift resolves, the true loss of muscle mass remaining in the legs is revealed that more slowly returns to the baseline or preflight level (see figure 6-2, leg during recovery on right side of graph for all three crewmembers). in the skylab 4 commander, the loss in leg volume appears to be nearly 300 cc. (figure 6-2, topmost graph). because the complement of exercise equipment for this mission was the largest (consisting of a cycle ergometer, passive treadmill, and the "mini gym", modified commercial devices that provided the capability for low-load resistive exercises) losses in muscle mass and strength were less than in the previous two missions of shorter duration. during the skylab program, exercises and exercise devices were added incrementally and the testing expanded with each mission. this produced a different exercise environment for each flight so that in reality, there were three separate but related orbital experiments, each with n=3. the results from each mission significantly affected the next. preflight and postflight evaluation of muscle strength was performed on the right arm and leg of each crewmember for all three skylab orbital missions by means of a cybex isokinetic dynamometer. the protocol completed on each crewmember included a thorough warm-up, and 10 maximum-effort full flexions and extensions of the arm at the elbow and of the hip and knee at an angular rate of 45° per second. the isokinetic leg strength from all three missions, as well as body weights and leg volumes, are presented in figure 6-3. figure 6-3. average changes in body weight, isokinetic leg strength, and leg volume of crewmembers on the three skylab missions. only the bicycle ergometer was used on skylab 2, the mk i and mk ii “mini gym” exercisers were added for skylab 3, and a passive “treadmill” was flown on skylab 4. the average work load per day on the cycle ergometer is also provided by mission for comparison. from reference. on skylab 2, only the bicycle ergometer was available for the in-flight exercise, with testing performed 18 days before launch and 5 days after landing. while it was realized that these times were too temporally remote from the flight, this was the best that could be achieved due to schedule constraints. by the time day 5 muscle testing was completed, some recovery in function had likely occurred; however, a marked decrement still remained. the decrement in leg extensor strength was nearly 25%; the arms suffered less but also exhibited marked losses (data not shown). the commander's arm extensors showed no loss, since he used these muscles in hand-pedaling the bicycle, being the only skylab crewmember to adopt this mode of arm exercise. this illustrated a fundamental point in muscle conditioning: to maintain the strength of a muscle, it must be stressed to or near the level at which it will have to function. leg extensor muscles, important in standing and providing propulsive forces during walking, are capable of generating forces of hundreds of pounds, while the arm extensor forces are measured in tens of pounds. forces developed in pedaling a bicycle ergometer are typically tens of pounds and are thus incapable of maintaining leg strength. the bicycle ergometer proved to be an excellent machine for aerobic exercise and cardiovascular conditioning, but it was not capable of developing either the type or level of forces needed to maintain strength for walking under 1g. immediately after skylab 2, work was started on devices to provide adequate exercise to arms, trunk, and legs. a commercial device, termed "mini gym", was modified extensively and designated "mk-i". only exercises that primarily benefited arms and trunk were achievable with this device. while forces transmitted to the legs were greater than those from the cycle ergometer, they were still limited to an inadequate level, since this level could not exceed the maximum strength of the arms, which represents a fraction of leg strength. a second device, designated "mk-ii", consisted of a pair of handles between which up to five extension springs could be attached, allowing development of maximum forces of 25 pounds per foot. these two devices were flown on skylab 3, and in-flight nutrition support and exercise time and food were increased. the crew performed many repetitions per day of their favorite maneuvers on the mk-i and to a lesser extent, on the mk-ii. also, the average amount of work done on the bicycle ergometer was more than doubled on skylab 3, with all crewmembers participating actively. it was perceived by skylb life scientists that a device that allowed walking and running under forces equivalent to earth gravity would provide more strenuous exercise. immediately after completion of skylab 2, work was begun on a treadmill for skylab 4. as mission preparation progressed, the launch weight of skylab 4 escalated so much that the final design of the treadmill was constrained by weight limitations. the final weight for the device was a mere 3.5 pounds. this passive device (figure 6-4) consisted of a teflon-coated aluminum walking surface attached to the skylab iso-grid floor. four rubber bungee cords provided an equivalent weight of about 80 kilograms (175 lbs) and were attached to a shoulder and waist harness worn by crewmembers during use. by angling the bungee cords to that the user was pulled slightly forward, an equivalent to a slippery hill was created. high loads were placed on some leg muscles, especially the calf, and fatigue was so rapid that the device could not be used for significant aerobic work because of the bungee/harness design. it was absolutely necessary to wear socks and no shoes to provide a low-friction interface to the teflon surface. figure 6-4. the first u.s. “treadmill” utilized during spaceflight was a passive device used only on the skylab 4 mission of 84 d duration. the high loading (175 lbs) via bungee cords provided more of a resistive rather than an aerobic modality. it consisted of a teflon-coated aluminum plate attached to the skylab isogrid floor. the exercising crewmember wore a waist and shoulder harness that attached to the iso-grid floor surrounding the treadmill plate by means of 4 bungee cords. socks had to be worn to provide a low-friction interface between the plantar surface of the feet and the teflon-coated treadmill plate. from reference. on skylab 4, the crew used the bicycle ergometer at essentially the same rate as on skylab 3, as well as the mk-i and mk-ii mini gym exercisers. in addition, they typically performed 10 minutes per day of walking, jumping and jogging on the treadmill. food intake had again been increased. upon their return to earth and even before muscle testing, it was apparent that the skylab 4 crewmembers were in very good physical condition. they were able to stand and walk for long periods without apparent difficulty on the day after landing (r+1), in contrast to the crewmembers from the earlier two missions. results of strength testing confirmed a surprisingly small loss in leg strength even after nearly 3 months of microgravity exposure (figure 6-3). in fact, knee extensor strength increased over the pre-flight level (figure 6-13). space shuttle a variety of investigations related to skeletal muscle function have been completed during the course of the space shuttle program (1981–2011). the most comprehensive of these was a suite of investigations accomplished during the extended duration orbiter medical project (edomp), which was carried out during 1989 – 1995 with missions of up to 16 days. studies most relevant to the risk on which this report focuses include the following detailed scientific objectives (dso): dso 475 – direct assessment of muscle atrophy and biochemistry before and after spaceflight dso 606 – evaluating concentric and eccentric skeletal muscle contractions after spaceflight dso 617 – evaluating functional muscle performance figure 6-5. first-generation or original space shuttle passive treadmill. from reference. the collective specific aim of dso 477 and dso 617 was to evaluate functional changes in concentric and eccentric strength (peak torque) and endurance (fatigue index) of the trunk, arms, and legs of crewmembers before and after flight. lido® dynamometer located at the johnson space center and at both the prime and contingency landing sites were used to evaluate concentric and eccentric contractions before and after flight. test subjects in this study exercised during flight for various durations, intensities and numbers of days on the original shuttle treadmill (figure 6-5) (as opposed to the edo treadmill, which flew on later shuttle missions and was the bases for the iss treadmill) as part of separate in-flight investigations. exercise protocols included continuous and interval training, with prescriptions varying from 60% to 85% of preflight maximal oxygen uptake as estimated from heart rate (hr) some subjects had difficulty in achieving or maintaining their target hr during flight. the brake (figure 6-5). a harness and bungee/tether system was used to simulate body weight by providing forces equivalent to an approximate 1-g body mass. subjects on this non-motorized treadmill were required to walk and run at a positive percentage grade to overcome mechanical friction. study participants were familiarized with the lido® test protocol and procedures about 30 days before launch (l-30), after which six test sessions were conducted. three sessions were completed before launch (l-21, l-14 and l-8 days) and three after landing (r+0, r+2 and r+7 to r+10 days). the muscle groups tested are shown in table 6-1. torque and work data were extracted from force-position curves. peak-torque, total work, and fatigue index measured in the three preflight test sessions were compared; when no differences were found between sessions, values from the three preflight sessions were