CARDIOVASCULAR ADAPTATIONS: CAN HYPERGRAVITY EXERCISE TRAINING MAINTAIN ORTHOSTATIC TOLERANCE?
A. Cardiovascular Adaptations to Microgravity
Exposure to microgravity (i.e. spaceflight) results in several changes in cardiovascular function that include elevated venous compliance and heart rate, lowered blood volume, central venous pressure and stroke volume, cardiac atrophy and attenuated baroreflex function (Frey 1987; Convertino and Hoffler 1992; Fritsch et al. 1992; Fritsch-Yelle et al. 1994; Convertino and Sandler 1995). These cardiovascular adaptations are not functionally apparent during spaceflight, but become dysfunctional for the astronauts upon return to a 1G environment, manifested as orthostatic intolerance (unable to stand continuously for 10 minutes) and up to a 25% reduction in maximal exercise capacity (Convertino and Hoffler 1992; Convertino 1992; Convertino 1994). Similar cardiovascular deconditioning is also observed during prolonged 6-degree head-down bed rest (i.e. simulated microgravity) (Convertino 1990; Crandall et al. 1994; Goldstein et al. 1995; Zhang et al. 2001). A variety of countermeasures have been developed, including saline “loading”, intermittent venous pooling (lower body negative pressure; LBNP), pharmacological manipulations and resistance training, but have had only limited success (Convertino and Hoffler, 1992).
For the cardiovascular system, current countermeasures do not effectively reproduce the vascular changes associated with a gravitational field. During upright posture on Earth, blood pressures are greater in the feet than at heart or head levels due to gravity’s effects on columns of blood in the body (Hicks and Badeer 1992). During exposure to microgravity, all gravitational blood pressures disappear. Presently, there is no exercise hardware available for space flight to provide this gravitational blood pressure to tissues of the lower body. Theoretically, an integrated countermeasure for extended exposure to microgravity should combine high loads on the musculoskeletal system (Whalen et al. 1988) with normal regional distributions of transmural pressure across blood vessels (Hargens et al. 1992) and stimulation of normal neuromuscular locomotor patterns.
An alternative approach to currently employed countermeasures is the use of a human powered, short-arm centrifuge (Fig. 1). The use of a short arm centrifuge as a countermeasure to microgravity was first considered in the 1960’s (White et al, 1965), however there has been no sustained research program devoted to evaluating the effectiveness of passive or active short-arm centrifugation. The use of “artifical gravity” as a countermeasure modality was recommended in a 1997 report of the NASA Task Force on Countermeasures, (NASA, 1997b) which concluded that a short-arm human powered centrifuge might be effective in protecting orthostatic tolerance. The NASA Task Force wrote:
“(artificial gravity) might replace the physiological stimuli to the cardiovascular system naturally provided in earth's environment, and forces greater than 1-G might be used to minimize the time required for countermeasure application.”
In addition, it was concluded that exercise-coupled +Gz training may be beneficial in protecting aerobic capacity;
“a human-powered centrifuge is a potential countermeasure designed to simultaneously apply cycle exercise (endurance) with head-to-foot gravity (+Gz) acceleration…………... The induced acceleration may potentiate the beneficial effects of exercise and other countermeasures on cardiovascular function after return from spaceflight.”
As a result of the Countermeasure Task Force Report and a recent NASA sponsored Workshop on Artificial Gravity, NASA has recently announced its intentions to support a vigorous animal and human research program on artificial gravity (AG) with available funding beginning in 2005, which will be sponsored by both NASA and its countermeasure research arm, the National Space Biomedical Research Institute. Thus, preliminary research emanating from the current proposal should posture the Irvine group as a pivotal component of this new NASA program.
Effects of Passive Hypergravity Training (HGTP):
It has been suggested that passive hypergravity training (HGTP) may partially counteract the negative physiological consequences of microgravity, although the results have sometimes been conflicting (White et al. 1965; Nicogossian et al. 1988). In humans, physiological studies on the effects of intermittent and chronic G-loading have focused primarily on cardiovascular performance (Cardus and McTaggart 1997; Hastreiter and Young 1997; Convertino et al. 1998; Iwasaki et al. 1998; Sasaki et al. 1999). A recent study (Convertino et al. 1998) investigated the effects of passive “G-training” on the baroreflex and orthostatic tolerance. In this study, subjects (6 men and 7 women) received repeated exposure on a centrifuge, 3 times per week for 4 weeks. The G-load started at +3Gz and advanced to +9-Gz (with G-suit protection) by the fourth week. The subjects were not exercising during the G-loading. These investigators concluded that G-training resulted in beneficial cardiovascular adaptations that either maintained or improved orthostatic tolerance, and the effect was limited only to the male subjects.
Iwasaki et al. (1998) hypothesized that the cardiovascular deconditioning and reduction of exercise capacity associated with microgravity exposure could be prevented by a daily 1 hr passive centrifugation at +2Gz. To test this hypothesis, twenty healthy male subjects underwent 4 day of 6 ° head-down-tilt bedrest, with ten subjects exposed to a +2-Gz load for up to 30 min twice per day (+Gz group) and the remaining subjects not exposed to a Gz load (the no-Gz group). The results indicated that cardiac sympathovagal balance tended to increase after bedrest in the no-Gz group, but no significant changes after bedrest in the +Gz group. Interestingly, maximal oxygen consumption decreased significantly to similar extent in both groups. It was suggested that passive +2-Gz exposure for 1 hr per day eliminates changes in autonomic cardiovascular control during simulated weightlessness. In addition, passive +Gz loading partly reversed hypovolemia induced by bedrest, but was not effective in preventing decreases in exercise capacity.
Effects of Exericse-Coupled Hypergravity Training (HGTX):
Only recently have several research groups (U.C. Irvine, MIT, NASA-Ames Research Center, Nagoya University) begun to explore the potential benefits of exercise-coupled hypergravity training (HGTX) as a potential countermeasure to microgravity. Coupled with exercise (Greenleaf et al. 1996; Kreitenberg et al. 1998), HGTX directly influences multiple physiological systems and therefore offers a promising countermeasure to the deleterious physiological effects of microgravity. For example, intermittent HGTX sessions may be beneficial in loading skeletal muscle and bone, while also maintaining the mechanisms responsible for orthostatic tolerance and aerobic performance and consequently HGTX may represent the “ultimate countermeasure”. A recent study (Sasaki et al. 1999) reports that intermittent +Gz (1.2 +Gz load at heart level, 30 min /day at 60 watts) partly reversed the reductions in plasma volume and changes in autonomic cardiovascular control associated with simulated microgravity. While these results are promising, the combined effects of aerobic training during G-loading on baroreflex function, orthostatic tolerance, and aerobic performance are relatively unknown, and determining these effects represents one of the major goals of the proposed research.
Currently, two general types of ground-based designs have been described in the literature. The first of these has been referred to as a human powered short arm centrifuge, and both the NASA-Ames Research Center (Greenleaf et al. 1996; Greenleaf et al. 1999) and the U.C. Irvine (Kreitenberg et al. 1998; Caiozzo et al. 2004) groups have been actively pursuing variations on this theme. The second approach has been described as a Twin Bike System (TBS), and was proposed by di Prampero and colleagues at the University of Udine, Italy (Antonutto et al. 1991; di Prampero 1994; di Prampero and Antonutto 1997; Antonutto and di Prampero 2003). To our knowledge, the TBS has not actually been built or tested. The NASA-Ames centrifuge is no longer operational, making the UC Irvine Space Cycle the only operational human powered centrifuge currently in the world. As such, the UCI group has the unique opportunity to become the leaders in the potential uses of hypergravity as a possible countermeasure to microgravity. Should our endeavors prove successful, it is highly possible that a modification of the UC Irvine Space Cycle will be used on the International Space Station and during missions to the Moon and Mars.
B. Significance
The significance of Space Cycle training is that it may prove to be an effective countermeasure in preventing the suite of adverse physiological effects associated with microgravity exposure. The significance of this innovation is that the Space Cycle concept may efficiently and quickly be demonstrated to be effective prior to its possible implementation in the International Space Station. Additionally, the Space Cycle has potential application for a number of other issues related to both microgravity and earth based conditions (Table 1).
For example, compared to standard aerobic training protocols, exercise-coupled hypergravity training may improve aerobic muscle performance and thus give rise to a new training regime known as “Gravity Doping”. Gravity doping may have important implications for preventing reductions in aerobic performance during space flight, may improve physical performance of military fighter pilots (Wojtkowiak et al. 1998) as well as practical applications for endurance athletes (cyclists and runners).
C. Hypotheses
The proposed research will use a human powered, short-arm centrifuge device (Space Cycle) and compare the effects of passive and exercise-coupled +Gz training (HGTP and HGTX respectively) and will test the following hypotheses:
Hypothesis I: HGTP and HGTX will enhance carotid sinus baroreflex function and orthostatic tolerance.
Hypothesis II: Under similar training regimes, HGTX will enhance aerobic performance compared to standard upright bicycle ergometry.