Frank M. Sulzman

Role of heat loss and heat production in generation of the circadian temperature rhythm of the squirrel monkey

To study heat production and heat loss in determination of the daily body temperature rhythm, we examined colonic temperature, skin (tail, foot and abdomen) temperatures and oxygen consumption in chair-restrained squirrel monkeys maintained in isolation in an environmental chamber with a 24-hr light-dark cycle (LD 12:12), maintained at a constant thermoneutral temperature (26 degrees C). In all experiments repeated high amplitude (2 degrees C) diurnal rhythms in colonic temperature were observed. Heat loss, estimated from changes in skin temperature, also displayed a circadian rhythm, although there was considerable variation in waveform. On average, a rhythm in heat production, indicated by changes in the rate of oxygen consumption, was also present. However, a large degree of variability was seen in oxygen consumption, and in several cycles from various animals there were no observable 24-hr rhythms. The circadian body temperature rhythm is thus not simply a consequence of daily changes in metabolism, but rather a regulated response that involves both heat production and heat loss.

Microcomputer monitoring of circadian rhythms

Abstract A method is described for conducting and evaluating circadian rhythm experiments. This procedure utilizes and Apple II + microcomputer which is configured to monitor multiple digital and analog data channels, and also to control environmental lighting schedules. This microcomputer system can also be used to analyze and plot the time series data.

Thermoregulatory responses of rhesus monkeys during spaceflight.

This study examines the activity, axillary temperature (T(ax)), and ankle skin temperature (Tsk) of two male Rhesus monkeys exposed to microgravity in space. The animals were flown on a Soviet biosatellite mission (COSMOS 1514). Measurements on the flight animals, as well as synchronous flight controls, were performed in the Soviet Union. Additional control studies were performed in the United States to examine the possible role of metabolic heat production in the T(ax) response observed during the spaceflight. All monkeys were exposed to a 24-h light-dark cycle (LD 16:8) throughout these studies. During weightlessness, T(ax) in both flight animals was lower than on earth. The largest difference (0.75 degree C) occurred during the night. There was a reduction in mean heart rate and Tsk during flight. This suggests a reduction in both heat loss and metabolic rate during spaceflight. Although the circadian rhythms in all variables were present during flight, some differences were noted. For example, the amplitude of the rhythms in Tsk and activity were attenuated. Furthermore, the T(ax) and activity rhythms did not have precise 24.0 hour periods and may have been externally desynchronized from the 24-h LD cycle. These data suggest a weakening of the coupling between the internal circadian pacemaker and the external LD synchronizer.

Circadian entrainment of the squirrel monkey by extreme photoperiods: interactions between the phasic and tonic effects of light.

To examine the role that the phasic and tonic aspects of the light-dark (LD) cycle play in entraining the circadian timing system of primates, squirrel monkeys (Saimiri sciureus) were exposed to 24 hr LD cycles in which the light duration (photoperiod) was varied from 1 sec to 23 hr. The monkeys were maintained in isolation and the circadian rhythm of drinking was monitored. The photoperiod was first gradually shortened until constant darkness was reached. Even in extremely short photoperiods of only one second of light per day, the drinking rhythm remained synchronized to the 24 hr period of the LD cycle. In the second set of experiments, the photoperiod was gradually lengthened until constant light was achieved. The drinking rhythm of all monkeys was synchronized by 21 hr photoperiods (LD 21:3), but free-ran in 23 hr photoperiods (LD 23:1) which provided a 1 hr dark pulse each day. The tonic effects of light may contribute to the difference between the ability to entrain to short versus long photoperiods. In constant darkness the free-running period was close to 24 hr, thus reducing the phase-resetting necessary to achieve entrainment to a 24 hr period by short light pulses. However, in constant light or in the long photoperiods which did not entrain (LD 23:1) the free-running period of the drinking rhythm was greater than 25 hr, thus requiring a much larger daily phase shift to achieve entrainment to a 24 hr period.

Circadian rhythms of drinking and body temperature of the owl monkey (Aotus trivirgatus)

The rhythms of drinking and body temperature of 4 male owl monkeys (Aotus trivirgatus) were examined under conditions of LD 12:12 (L = 100 lx, D = 0.1 lx), DD (0.1 lx) and LL (100 lx). For all 4 monkeys, the circadian pattern expressed in LD 12:12 continued in DD, with a free-running period averaging 23.6 hr. In LL the circadian component of both rhythms decayed and, in one monkey, a low frequency pattern arose. In at least two aspects, masking and persistence, the owl monkey circadian timing system appears to be unlike that of its diurnal relative, the squirrel monkey. Circadian rhythms of owl monkeys also differ in some respects from those of other nocturnal mammals.

Cellular autonomy of theGonyaulax circadian clock

Because of the long term persistence of free-running circadian rhythms in populations of unicells, several investigators have considered, but not demonstrated, a possible role for intercellular interaction in maintaining synchrony between individual cells. The experiments described here were designed to test more critically the possibility that there is interaction between cells, including those possessing only small phase differences. None was detected; the bioluminescent glow of the mixed cultures matched the algebraic sum of the independent control cultures.

The biological clock of Neurospora in a microgravity environment.

The circadian rhythm of conidiation in Neurospora crassa is thought to be an endogenously derived circadian oscillation; however, several investigators have suggested that circadian rhythms may, instead, be driven by some geophysical time cue(s). An experiment was conducted on space shuttle flight STS-9 in order to test this hypothesis; during the first 7-8 cycles in space, there were several minor alterations observed in the conidiation rhythm, including an increase in the period of the oscillation, an increase in the variability of the growth rate and a diminished rhythm amplitude, which eventually damped out in 25% of the flight tubes. On day seven of flight, the tubes were exposed to light while their growth fronts were marked. Some aspect of the marking process reinstated a robust rhythm in all the tubes which continued throughout the remainder of the flight. These results from the last 86 hours of flight demonstrated that the rhythm can persist in space. Since the aberrant rhythmicity occurred prior to the marking procedure, but not after, it was hypothesized that the damping on STS-9 may have resulted from the hypergravity pulse of launch. To test this hypothesis, we conducted investigations into the effects of altered gravitational forces on conidiation. Exposure to hypergravity (via centrifugation), simulated microgravity (via the use of a clinostat) and altered orientations (via alterations in the vector of a 1 g force) were used to examine the effects of gravity upon the circadian rhythm of conidiation.

Physiological adaptation to space flight

In space, adaptive physiological changes have been observed in virtually all body systems, but how far these changes progress with time is not known. Their time course demonstrates variable patterns; some systems show evidence of gradual and progressive change. Biomedical postflight data have shown that a compensatory period of readaptation to one gravity is required after space flight, with longer intervals required for longer missions. Consistent readaptation trends include orthostatic intolerance and neurovestibular difficulties. For the long-duration missions of the exploration era, it is critical to determine the extent to which deleterious changes (e.g., bone loss and possible immunological changes) can be reversed upon return to earth. Radiation protection is another critical enabling element for missions beyond low earth orbit. Radiation exposure guidelines have not been established for exploration missions. Currently our experience is insufficient to prescribe countermeasures for the stay times associated with a lunar base or a mission to Mars. Artificial gravity may provide a solution, but the level and duration of exposure necessary to prevent deconditioning must be determined. Central issues for medical care in remote settings are preventive, diagnostic, and therapeutic care and the minimization of risk.

Primate Circadian Rhythms

There are prominent daily changes in physiology and behavior of primates, which are timed by the circadian timing system-a set of physiological systems that provides the body with temporal organization. This article describes how human and nonhuman primates have been used to elaborate the structure and function of the circadian timing system. The relevance of the circadian rhythmicity to health is also discussed. (Accepted for publication 28 February 1983)

THE BIOASTRONAUTICS CRITICAL PATH ROADMA P (REV. 2): BIOMEDICAL RISK ASSESSMENT FOR SPACE EXPLORATION MI SSIONS

The Bioastronautics Cri tical Path Roadmap (BCPR) project was initiated in 1997 to identify biomedical risks in human space exploration, to document and guide risk resolution and to communicate to investigators those human life sciences research goals most relevant to NASA. In a nticipation of the Presidents new initiative for space explorations announced in January 2004, BCPR discipline -area experts and bioastronautics managers from NASA and the National Space Biomedical Research Institute (NSBRI) jointly established sixteen tea ms to consider the biomedical risks inherent in likely future mission scenarios in the terms of their initiating events, risk factors and outcomes; enabling questions; and temporal and technology interrelationships. These discipline -based teams are in fiv e major categories: Advanced Human Support Technologies; Autonomous Medical Care; Behavioral Health and Performance; Human Health and Countermeasures; and Radiation Impacts and Countermeasures. Three probable future piloted space flight scenarios are anal yzed: one - year continuous tours of duty aboard the International Space Station; one -month excursions to the lunar surface; and thirty -month expeditions to Mars. The BCPR project also addresses processes for prioritizing, implementing and assessing the tas ks to mitigate the identified risks. After the conclusion of a year -long review of its content and processes by committees of the National Research Council, it is expected that the BCPR will guide NASAs assessment and mitigation of the risks to astronau t health and operational performance during increasingly challenging space exploration missions over the next few decades.