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Tipton, Charles M.

Publications and source records attributed to Tipton, Charles M..

Neuroendocrine and Immune System Responses with Spaceflights

Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T-lymphocytes and natural killer cells are decreased with post-flight conditions. Of the lymphokines, interleukin-2 production, lymphocyte responsiveness, and the activity of natural killer cells are consistently reduced post-flight. Limited head-down tilt (HDT) data suggest it is an effective simulation model for microgravity investigations. Neuroendocrine and pharmacological countermeasures are virtually nonexistent arid should become high priority items for future research. Although exercise has the potential to be an effective countermeasure for various neuroen-docrine-immune responses in microgravity, this concept must be tested before flights to Mars are scheduled.

Tipton, Charles M.↗

Muscle glucose uptake in the rat after suspension with single hindlimb weight bearing

An examination is conducted of the effect of nonweight-bearing conditions, and the systemic influences of simulated microgravity on rat hindlimb muscles. The results obtained suggest that the increases in hindlimb muscle glucose uptake and extracellular space associated with simulated microgravity persist with hindlimb weightbearing, despite the prevention of muscle atrophy. The mechanism (or mechanisms) responsible for these effects are currently unknown.

Stump, Craig S.↗

Influence of simulated microgravity on the maximal oxygen consumption of nontrained and trained rats

The effects of microgravity and endurance training (TR) on maximal O2 consumption was investigated in trained and nontrained (NT) rats subjected to head-down suspension (HDS) by comparing maximal O2 consumption, treadmill run time (RT), and mechanical efficiency (ME) of treadmill running in HDS rats, both NT and TR, and in respective cage controls. It was found that HDS for 28 days was associated with significant reduction in absolute maximal O2 consumption in both TR and NT rats. Relative maximal O2 consumption, however, was significantly reduced in TR but not NT rats. Reductions in RT and ME occurring in both TR and NT rats after 28 days of HDS were similar. The TR rats exhibited greater diuretic, natriuretic, and kaliuretic responses to HDS than the NT rats.

Woodman, Christopher R.↗

Effects of insulin and exercise on rat hindlimb muscles after simulated microgravity

The effect of simulated microgravity on the insulin- and exercise-stimulated glucose uptake and metabolism in the hindlimb muscles of rats was investigated using three groups of rats suspended at 45 head-down tilt (SUS) for 14 days: (1) cage control, (2) exercising (treadmill running) control, and (3) rats subjected to suspension followed by exercise (SUS-E). It was found that the suspension of rats with hindlimbs non-weight bearing led to enhanced muscle responses to insulin and exercise, when these stimuli were applied separately. However, the insulin affect appeared to be impaired after exercise for the SUS-E rats, especially for the soleus muscle.

Stump, Craig S.↗

Influences of chemical sympathectomy, demedullation, and hindlimb suspension on the V(O2)max of rats

The contributions of catecholamines from the adrenal medulla to the reduction in maximal oxygen consumption is investigated in chemically sympathectomized rats. The rats are injected with saline and chemically sympathectomized, and approximately half of the rats are surgically demedullated. The subjects undergo head-down suspension for two weeks and are examined in terms of submaximal mechanical efficiency, treadmill run time, and maximal oxygen consumption. Rats with adrenal medullas and injected with saline demonstrate reduced levels of maximal O consumption, whereas chemically sympathectomized rats with adrenal medullas showed no significant reduction. Reduced levels of maximal O consumption is also noted in the sympathectomized demedullated rats. The paper concludes that circulating epinephrine enhances the attenuation of the decrease in the maximal O consumption caused by chemical sympathectomy.

Woodman, Christopher R.↗

Effect of 29 days of simulated microgravity on maximal oxygen consumption and fat-free mass of rats

Effects of a 29-days exposure to simulated microgravity on the values of maximal oxygen consumption and fat-free mass (FFM) and on the mechanical efficiency of running were investigated in rats randomly assigned to one of three regimens: head-down suspension (HDS) at 45 deg, horizontal suspension (HS), or cage control (CC). Before suspension and on days 7, 14, 21, and 28, five exercise performance tests were carried out, with measurements related to maximal oxygen consumption, treadmill run time, and mechanical efficiency. It was found that maximal oxygen consumption of both HDS and HS groups decreased significantly at day 7, after which the HDS rats remained decreased while the HS rats returned to presuspension values. Apparent mechanical efficiency in the HDS and HS groups decreased by 22-35 percent during the experimental period, and FFM decreased significantly.

Woodman, Christopher R.↗

Influences of chemical sympathectomy and simulated weightlessness on male and female rats

Consideration is given to a study aimed at determining whether the sympathetic nervous system is associated with the changes in maximum oxygen consumption (VO2max), run time, and mechanical efficiency observed during simulated weightlessness in male and female rats. Female and male rats were compared for food consumption, body mass, and body composition in conditions of simulated weightlessness to provide an insight into how these parameters may influence aerobic capacity and exercise performance. It is concluded that chemical sympathectomy and/or a weight-bearing stimulus will attenuate the loss in VO2max associated with simulated weightlessness in rats despite similar changes in body mass and composition. It is noted that the mechanisms remain unclear at this time.

Woodman, Christopher R.↗

Mechanistic studies on reduced exercise performance and cardiac deconditioning with simulated zero gravity

The primary purpose of this research is to study the physiological mechanisms associated with the exercise performance of rats subjected to conditions of simulated weightlessness. A secondary purpose is to study related physiological changes associated with other systems. To facilitate these goals, a rodent suspension model was developed (Overton-Tipton) and a VO2 max testing procedure was perfected. Three methodological developments occurred during this past year deserving of mention. The first was the refinement of the tail suspension model so that (1) the heat dissipation functions of the caudal artery can be better utilized, and (2) the blood flow distribution to the tail would have less external constriction. The second was the development on a one-leg weight bearing model for use in simulated weightlessness studies concerned with change in muscle mass, muscle enzyme activity, and hind limb blood flow. The chemical body composition of 30 rats was determined and used to develop a prediction equation for percent fat using underwater weighing procedures to measure carcass specific gravity and to calculate body density, body fat, and fat free mass.

Tipton, Charles M.↗

Influence of single hindlimb support during simulated weightlessness in the rat

A study was carried out to develop and evaluate a hindlimb suspension model, making it possible to differentiate the effects of non-weight bearing by hindlimbs per se from the systemic influence of simulated weightlessness. A support platform was designed which allowed the animal to maintain one hindlimb in a posture similar to the hindlimbs of the control animals at rest and to maintain one hindlimb in a posture similar to the hindlimbs of the control animals, providing a support for the animal to contract or stretch hindlimb muscles against at any time during suspension. The results of this study indicated that hindlimb support during head-down suspension will maintain muscle-mass/body-mass ratios, glycogen concentration, and blood flow. However, it will not prevent the loss in citrate synthase activity associated with conditions of simulated weightlessness.

Stump, Craig S.↗

Effect of hindlimb suspension on cardiovascular responses to sympathomimetics and lower body negative pressure

To determine whether hindlimb suspension is associated with the development of cardiovascular deconditioning, male rats were studied before and after undergoing one of three treatment conditions for 9 days: (1) cage control (n = 15, CON), (2) horizontal suspension (n = 15, HOZ), and (3) head-down suspension (n = 18, HDS). Testing included lower body negative pressure administered during chloralose-urethan anesthesia and graded doses of sympathomimetic agents (norepinephrine, phenylephrine, and tyramine) administered to conscious unrestrained animals. Both HDS and HOZ were associated with a small decrease in the hypotensive response to lower body negative pressure. The HOZ group, but not the HDS group, exhibited augmented reflex tachycardia. Furthermore, both HDS and HOZ groups manifested reduced pressor responses to phenylephrine after treatment. These reductions were associated with significantly attenuated increases in mesenteric vascular resistance. However, baroreflex control of heart rate was not altered by the treatment conditions. Collectively, these results indicate that 9 days of HDS in rats does not elicit hemodynamic response patterns generally associated with cardiovascular deconditioning induced by hypogravic conditions.

Overton, J. Michael↗

Influence of simulated weightlessness on maximal oxygen uptake of untrained rats

The purpose of this study was to determine the effect of hindlimb suspension on maximal oxygen uptake of rodents. Male Sprague-Dawley rats were assigned to head-down (HD) suspension, horizontal (HOZ) suspension, or cage (C) control for 6-9 days. Rats were tested for maximal oxygen uptake before and after surgical instrumentation (Doppler flow probes, carotid and jugular cannulae), and after suspension. Body weight was significantly decreased after suspension in both HD and HOZ groups, but was significantly increased in the C group. Absolute maximal O2 uptake (ml/min) was not different in the C group. However, because of their increased weight, relative maximal O2 uptake (ml/min per kg) was significantly reduced. In contrast, both relative and absolute maximal O2 uptake were significantly lower, following suspension, for the HD and HOZ groups. These preliminary results support the use of hindlimb suspension as an effective model to study the mechanism(s) of cardiovascular deconditioning.

Overton, J. Michael↗