Wednesday, November 12, 2014

Torpor in Space Travel

With existing tested technology the fastest transit time between Earth and Mars is during the perihelion (although Mars has only come within 34.8 million miles in 2003 versus the 33.9 million of the actual perihelion) resulting in a minimum transit estimate of approximately 180 days. Some believe that six months of monotonous space travel would be a significant psychological detriment on the future colonists, thus they recommend investigating a strategy of inducing torpor initiated through a therapeutic hypothermia methodology. Therapeutic hypothermia involves lowering an individual’s body temperature and is commonly reserved for medical emergencies involving cardiac arrest and various embolisms like strokes. It is thought that the decrease in temperature reduces biological metabolism, which reduces tissue damage born from oxidation and excess neuronal excitation triggered by a lack of regulated blood flow. Note that torpor is a state of decreased physiological activity through a reduced body temperature reaching a lower limit of survivable metabolism. Due to these changes torpor is commonly viewed as a state of consciousness distinct from wakefulness, sleep or coma.

The chief method to induce therapeutic hypothermia is a controlled reduction of core temperature through one of three possible methods: 1) invasive cooling usually involving an IV of cooled fluids; 2) conductive cooling where the body is placed in contact with cold compresses, typically cold gel pads and/or wet blankets; 3) convective cooling where specific gases evaporate and pass into the nasal and oral cavity leading to a reduction in body temperature.

Of the three conductive cooling is typically the most widely utilized because of its effectiveness and simplicity. Some researchers have explored new and more direct chemical methods to develop a hibernation state like activating adenosine receptors or using hydrogen sulfide to reduce cellular demand for oxygen.1 Others have thought to induce hibernation through synaptic manipulation, but that method is probably best avoided due to brain plasticity issues, which could result in temporary or permanent brain damage.

While the above methods are viable for inducing therapeutic hypothermia, a significant concern for a “hibernated” space travel strategy is that cooling/cryogenic strategies are in their infancy, thus most therapeutic hypothermia states rarely exceed 24-hrs and the longest is only about 14-days, a long cry from the 180-days of a trip to Mars. In addition to improving cooling methodology, temperature monitoring needs to be improved to incorporate a better realization of core temperature versus localized temperatures from specific measurement points (bladder, rectal, tympanic or esophageal). In general practice these specific measurement points tend to correlate with core temperature, but long-term hypothermia inducement will more than likely require more universal tracking of acute internal temperature changes. In addition to lowering the core body temperature one must neutralize shivering otherwise metabolic rates will not decrease sufficiently to realize the associated therapeutic benefits. Currently shivering is commonly controlled through the application of desflurane, pethidine, and/or meperidine.2

The most obvious non-psychological benefit of placing a colonization crew in torpor is a significant reduction in food/consumables for transit and the potential reduction in overall consumables. The reason that the overall reduction may only be a possibility is determined by whether or not the non-consumption during transit will transfer to “on Mars” consumption. For example suppose 1 ton of food (not mission specific just a number for example purposes) is loaded for a standard non-torpor mission and among the four colonists a total of 4 pounds is consumed daily. Over the course of the trip approximately 760 pounds of food will be consumed leaving 1,240 pounds of food for consumption on Mars. In a torpor mission two strategies are available: 1) only 1,240 pounds of food will be loaded saving 760 pounds for something else or just straight cost savings; 2) 1 ton of food is loaded with no cost savings, but an additional 760 pounds of food will be available for consumption on Mars.

Secondary benefits come from the possible reduction in the required pressurized volume in the living quarters and the elimination of ancillary crew accommodations, which could reduce the size of the transport craft reducing the total cost of the mission or increase the ability to add subsystem redundancy and/or more radiation shielding at similar costs. Basically the chief non-psychological benefit for a torpor mission is a greater flexibility in distributing what types of materials are loaded for a Mars mission and the final mission cost.

While torpor proponents would suggest that there are a few bugs left to work out, but prospects for such a strategy appear viable, in actuality there remain two significant problems that must be overcome before a torpor strategy can be viewed as viable. The first problem, the most pressing, is muscular atrophy born from general space travel and the second problem is overall safety. The principle responsibility of skeletal muscle is to govern movement of all voluntary muscle, including the maintenance of posture. Due to human evolution on Earth skeletal muscle has to move parts of the body against gravity, thus there is a strong relationship between the size and metabolism of skeletal muscle and the gravitational force of the existing environment.

Skeletal muscle is comprised of bundles of muscle fibers, which are large cells formed through the fusion of many individual cells during development. Most skeletal muscles consist of myfibrils, which are cylindrical bundles of either thicker myosin filaments or thinner actin filaments, and form contractile elements (sarcomeres). Sarcomeres are separated into Z discs (the ends) along with A and I bands where A bands are largely comprised of myosin and I bands are largely comprised of actin. Some have additionally defined a buffer zone of sorts (H zone).
The general methodology for muscle contraction is the sliding filament model.

Muscle fibers generate active and passive mechanical forces to overcome gravity to ensure proper posture, movement and biological function. Active muscle tension is derived from muscle contractions leading to shortening of myofiber’s sarcomeres whereas passive tension occurs through sarcomere stretching reducing their level of overlap.3-5 It appears that slow twitch muscle fibers are more susceptible to the change in gravitational force versus fast twitch muscle fibers.6,7 This difference in degradation can be troublesome because not only is slow twitch muscle more associated with posture, but is also associated with muscular endurance. In addition to muscle atrophy there is a serious drop-off (>50%) in protein synthesis rates and a significant loss of calcium balance.8-10 Whether or not this loss of calcium is due to actual direct losses or indirect absorption losses (i.e. a lack of Vitamin D) is unknown.

The change in protein synthesis rate is further compromised by activation of protein degradation rates.11 One of the major pathways responsible for atrophy is the ATP-dependent ubiquitin/proteasome pathway with the most important feature being E3 ubiquitin ligase due to its specificity in targeting certain proteins for elimination.12

Torpor proponents believe that the negative influence of atrophy, which will be much worse for individuals in torpor because of the lack of ability to exercise, can be neutralized through the use of neuromuscular electrical stimulation (NMES). NMES induces muscle contraction using electric impulses born from electrodes on the skin in close proximity to the desired muscle to be stimulated. This system works because the electrical stimulation from the electrodes mimics neuronal stimulation derived from action potentials.

Proponents view NMES as an effective strategy for increasing muscle mass, muscle endurance, maximal voluntary strength, neural drive and oxidative metabolism, which could also increases immune system activity.13 With these changes proponents believe that NMES could have a positive effect on reducing muscular atrophy. While NMES may have the ability to induce these increases relative to not exercising, there are two important questions that have yet to be answered. The first question is whether or not NMES can outperform the current exercise regime utilized by ISS astronauts?

For example in one study despite aerobic exercise for 5 hours per week at moderate intensity and resistance exercise performed 3-6 days per week at 2 hours per day calf muscle volume in astronauts decreased by 13%, peak power decreased by 32%, force-velocity reduced between 20 to 29% and there was a 12 to 17% increased shift between fast twitch muscle to slow twitch muscle.14 This study and others support the idea that current vigorous exercise designs are not sufficient to ward off significant muscle atrophy hence why most ISS habitation is a maximum of six months.

Unfortunately there is little evidence to suggest that NMES is superior to voluntary endurance and strength exercises because there is almost no evidence comparing the two methodologies in well-designed and properly controlled studies. Another concern related to this comparison is the lack of specifics regarding the biological changes that occur when an individual is exposed to long-term NMES. Finally the second important question creates a logical belief that NMES is not equal or greater than normal voluntary exercise.

This second major question is how does NMES affect muscular fatigue? In humans despite using several different stimulation patterns, frequencies under 16 Hz were not strong enough to produce a contraction that extending a quadriceps to at least 40 degrees.15 Therefore, most stimulation methodologies, depending on the overall type of intervention, utilize frequencies between 20-50 Hz.16,17 This magnitude of frequency creates a non-selective, spatially fixed (due to the continuous nature of the pulse) and synchronous motor unit recruitment.18-20 The immediate interesting element is that these characteristics of recruitment are different from that which occurs in voluntary muscle contraction, which is governed by the Henneman’s size principle.21,22

The evolution of muscle firing and recruitment is shown in the size principle where smaller more fatigue-resistant motor units are activated first followed by larger units if necessary; these larger units can also replace de-recruited units that drop out due to fatigue.23 This process creates an efficient firing recruitment system that maximizes muscular endurance and reduces overall fatigue and its negative effects. However, NMES has a more random simultaneous recruitment instead of organized sequential recruitment, which eliminates fatigue-reducing mechanisms. Unfortunately the level of this non-selective recruitment is not uniform, but seems almost dependent on what particular muscle group is being stimulated.24,25 Another concern with this change in recruitment is how non-selective recruitment for approximately 6 months could influence the long-term functionality of normal voluntary movement when NMES is eliminated after arriving on Mars. Basically will there be any long-term negative effects when “retraining” muscles for size recruitment rather than random recruitment?

Also this increased rate of fatigue may explain why fast twitch muscle fiber tends to morph into slow twitch muscle in NMES patients13 as slow twitch muscle is more resistant to fatigue. This conversion is troublesome because as discussed above, for some reason slow twitch muscle tends to be more prone to atrophy versus fast twitch muscle. Thus this muscle conversion could handicap the ability of NMES to ward off muscle atrophy versus voluntary muscle exercises.

A third concern is that surface-stimulating electrodes apply current directly beneath the surface of the electrode. However, because the electrodes are on the surface the currents they produce need to travel through various subcutaneous tissues with a diverse level of resistances. One study calculated that this impulse was only able to reach superficial motor units 10-12 mm deep and had difficulty reaching the larger motor units deeper in tissue.26 Therefore, an increase in pulse width or amplitude would be needed to improve penetration to reach these other motor units. This “incomplete” penetration may also explain the non-selective motor unit recruitment seen from NMES. Another problem with the localized influence of the electrodes in NMES is the potential damaging effect of the isometric contractions. Multiple studies report significant increases in creatine kinase, macrophage infiltration, z-line disruption and increases in muscle soreness.27-30

A fourth possible issue with NMES is the lack of full neuronal activation. With the stimulation origin focused on a single location at a specific muscle group there is the potential for reduced neuronal coordination with other critical systems. For example some believe that one of the keys to effective muscular endurance and overall muscle health is not only consistent muscle exercise, but also the sequence that begets the activation of the muscle including proper interaction between the muscle, the heart and respiratory systems, something that escapes current NMES protocols. Basically for voluntary muscle movement the neuronal signals originate in the brain and are able to coordinate the appropriate timing on heart, respiratory and other important associated systems whereas NMES skips this activation and relies on feedback to start the process.

Some have thought to increase the effectiveness of exercise to neutralize atrophy through increasing circulating concentrations of growth hormone, various other steroids and/or insulin-like growth factor 1 (IGF-1), which is the main effector molecule for growth hormone, by either augmenting muscle growth or using proteolytic inhibitors to reduce muscle degradation.14 There are some preliminary studies that demonstrate a synergistic effect between growth hormone and exercise in reducing atrophy, but a lot more work needs to be done to establish a positive correlative protocol. For example chronic delivery of growth hormones and other protein growth factors is troublesome because they have short half-lives and damaging side effects in either large quantities or over long periods of time, which right now is required to augment muscle growth.31,32

When addressing safety a chief concern is about the total time an individual could remain in torpor (approximately 180 days). Some advocate hibernation in shifts where one individual is always awake and switches with another individual every x number of days. Even without a defined length of time for being both awake and in hibernation, the biggest immediate concern with this recommendation is how the body would cope with constantly moving between a hibernated and non-hibernated state. For example how would various enzymes and other proteins, which have a very short temperature range of activation, handle 6-7 cycles of being at 92 degrees C for 21 days and then 98.6 for 7 days? While some could argue that hibernating mammals, like bears, periodically roust themselves safely from torpor during their hibernation cycles before reentering hibernation this argument appears invalid because these creatures have evolved to hone the safe application of this behavior, humans have not.

Also the process of therapeutic hibernation is similar to flying in a plane where the most dangerous aspects are the entrance (takeoff) and awakening (landing); numerous entrances and awakenings from hibernation would only increase the probability of a critical failure resulting in serious health damage or death. Overall at this moment it is difficult to argue in favor of a hibernation “shift” strategy. If one is concerned about relying on 100% automation, it stands to reason that one person should remain active for the entire flight with remaining crewmembers in torpor.

Another question regarding the application of torpor is the loss of in-transit preparation time. While it is ideal that all of the colonists are sufficiently prepared for their specialized tasks when arriving on Mars, there is a significant unknown to how well they would retain this knowledge and training. During the transit, it is reasonable to suggest that most of the time would be spent honing their abilities and skills that will be applied upon arriving on Mars to reduce the probability of critical errors during the colonization process. In a torpor state this additional preparation time is lost. Therefore, it is important to consider how knowledge and skills will be retained both in general and within a torpor state.

While the benefits of placing numerous, if not all, astronauts traveling to Mars in a torpor state for the duration of the transit appear attractive there are two major issues that must be addressed. First, the safety of the methodology must be thoroughly analyzed. On its initial face determining safety may be quite difficult for two reasons: 1) the process of therapeutic hypothermia has only ever been significantly tested on people with severe injuries, not people with high levels of health, a characterization that would comprise all prospective Mars colonists. However, what type of “healthy” individual would volunteer to be placed in a 1-month, 2-month, 3-month, etc. torpor state to determine the positive and negative effects on his/her body? 2) all major testing would more than likely occur on Earth to ward off accidental loss of human life due to the ability to immediately act if anything goes wrong; however, without observing how the body would react in a microgravity environment versus the natural gravity environment of Earth creates holes in the knowledge of how the body changes over time while in hibernation during travel.

Second, it is well known that muscle atrophy is one of the biggest threats to the success of a long-term off-Earth colonization mission. At the moment there is little reason to suspect that NMES will be able to ward off atrophy at a similar level to existing exercise protocols let alone surpass their effectiveness. It does little good to save food and space in transit when colonists will simply suffer major muscle injuries upon waking up and moving around for the first time in half a year. Also the question of erosion of colonist skills is one that must be addressed because it would be unnecessarily risky to expect colonists to re-learn skills after landing on Mars. Overall while the idea of inducing a torpor state in colonists during transit to Mars is an interesting one there are numerous smaller questions as well as a few larger questions that must still be addressed as well as some potential technology hurdles before this strategy can be considered viable.


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