Melatonin: aeromedical, toxicopharmacological, and analytical aspects.

Melatonin, a pineal hormone present in the blood of humans and other species, has a distinct diurnal variation in its biosynthesis and, therefore, in its concentration. This variation has suggested the possibility of a regulatory function in day/night-dependent physiological processes such as sleep and has led scientists to explore the effects of administered melatonin on the modulation of circadian rhythms. For the self-treatment of sleep disorders and other benefits, melatonin use has been extolled to the extent that 20 million new consumers were added to the U.S. retail market in 1995. Its principal aeromedical application has been in the experimental treatment of jet-lag effects. For aircraft passengers, melatonin administration at destination bedtime appears to improve sleep quality and to decrease the time required to reestablish normal circadian rhythms. For international aircrews that travel through multiple time zones without time to adapt to new environments, taking melatonin before arriving home may further impair already disturbed circadian rhythms. Its use to adjust to shiftwork changes by air traffic controllers, aircraft maintenance workers, and support personnel is even more controversial. Limited studies suggest that giving this hormone to shift workers should be done only under controlled conditions and that taking it at the wrong time may actually impair job performance. Because of its possible interaction with certain medications and the changes in its concentrations observed in some clinical conditions, the practitioner must exercise caution during the medical certification of airmen. The variations in the concentration of melatonin can be effectively determined by radioimmunoassay, high-performance liquid chromatography, and gas chromatography-mass spectroscopy analytical techniques. These techniques are capable of measuring the human daytime (10 pg/mL) and nighttime (30-120 pg/mL) melatonin in plasma/serum. Melatonin measurements in victims of accidental death may allow forensic scientists and accident investigators to use the relationship between its concentration and the time of day when death occurred. The most accurate estimations of the time of death result from analysis of melatonin content of the whole pineal body, whereas less accurate estimates are obtained from serum and urine analyses. Pineal levels of melatonin are unlikely to be altered by exogenous melatonin, but its blood and urine levels would change. High blood levels in a daytime crash victim would suggest exogenous supplementation. The possible interfering effects of postmortem biochemical processes on melatonin concentrations in whole blood and in other tissues are not well understood, and there is a need for the continuing research into melatonin's chronobiological properties to define its proper applications and limitations. The indiscriminate use of melatonin by aviation professionals may pose unacceptable safety risks for air travel.

Toxicological findings in Federal Aviation Administration general aviation accidents.

Blood, urine, and tissue specimens were received from 377 Federal Aviation Administration (FAA) aviation fatalities during fiscal year 1989. Carbon monoxide at less than 10% saturation was found in 94% of the cases, and cyanide at less than 0.5 mg/L was found in 96% of the cases. Ethanol at greater than 10 mg/dL was found in 14.8% of the cases, but only 4.5% were determined to be due to ethanol ingestion from toxicological findings. Excluding nicotine and ethanol, 12.6% of the cases were positive for one or more drugs. Acetaminophen and salicylate were the most frequently found drugs. Cannabinoids were found in 1.3% of the cases and benzoylecgonine in 1.6%. There was minimal use of therapeutic drugs that cause central nervous system depression or stimulation. These results show no consistent pattern of drug involvement in civilian aviation fatalities.

Response capability during civil air carrier inflight medical emergencies.

Expanded civil aircraft medical emergency kits have been mandated on U.S. carriers since August 1986. Airlines provided the Federal Aviation Agency reports on medical kit usage and outcomes of the associated medical emergencies; 1,016 inflight medical events during the period August 1, 1986, through July 31, 1987, were available for review. Physicians responded to the emergencies in over 63% of the occurrences; the two most prevalent presenting situations were chest pain and syncopal episodes. Nine passengers died on board aircraft, and at least three deaths occurred postlanding. A minimum of 89 of the total cases resulted in flight diversions. The sphygmomanometer (739 cases) and stethoscope (734 cases) were the most frequently used kit items; oropharyngeal airways were utilized in 14 cases. Since standardized reporting formats are not required, evaluation of response capability remains incomplete.

Relative efficacy of the proposed Space Shuttle antimotion sickness medications.

Space motion sickness has been estimated as affecting between 1/3 and 1/2 of all space flight participants. NASA has at the moment proposed a combination of promethazine and ephedrine (P/E) and one of scopolamine and dextroamphetamine (S/D), both given orally, as well as a transdermally applied scopolamine (TAS), as preventive and ameliorative measures. The reported double-blind study, tests the early phase actions and efficacy of the transdermal scopolamine (Transderm (TM)-V of ALZA Corporation) and compares these in detail to the oral medications. Motion sickness resistance was tested by standardized head movements while accelerating at 0.2 degree/sec2 to a maximum rotation of 240 degrees/sec, with an intermediate plateau of 10 min at 180 degrees/sec. To permit weighting motion sickness protection against other system influences, cardiovascular, psychological (subjective and objective), and visual parameter changes were documented for the three therapeutic modes. The relative impact of the various modalities on operational and experimental components of space missions is discussed. A comparison to intramuscularly administered promethazine (a backup therapeutic mode suggested for Space Shuttle use) is also included.

Cell morphological, ontogenic, and genetic reactions to 0-g simulation and hyper-g.

Organisms use gravity for spatial orientation, and differentiation into species during evolution follows geological processes which are caused by gravity. On the other hand, the task of most organismic functions which have or may have a relation to gravity is to compensate gravity. Furthermore, today it is very obvious that organisms do not disintegrate under the conditions of weightlessness, at least for the currently tested durations. These previous statements indicate a large field of still unknown regulation and adaptation mechanisms. Experiments to simulate weightlessness on the fast clinostat and with hyper-g show a highly developed ability of the genetic chain and of differentiating cells in being autonomous against mechanical stresses caused by outer accelerations. Nevertheless, different strong and slight changes of different tested end points were found. The question remains if the cells react actively or only passively.

Cardiovascular and biochemical response to simulated space flight entry.

Twelve men and 12 women were exposed to two types of short-duration (6 h) space flight entry simulation: bedrest (no head-down tilt) and water immersion (to the neck). Preceding and following the simulation, orthostatic tolerance testing using LBNP (Lower Body Negative Pressure) was performed. Male LBNP tolerance was greater than female LBNP tolerance at all four comparison points (pre- and post-bedrest, pre- and post-water immersion); whereas the short-duration bedrest reduces female LBNP tolerance about as effectively as water immersion, only water immersion leads to marked LBNP intolerance in the male subjects. If the water immersion model simulates zero G, loss of male and female orthostatic tolerance will be about equal after short-duration space flight. On the other hand, the bedrest simulation would indicate a greater loss of orthostatic tolerance for females.

A new application of LBNP to measure orthostatic tolerance before and after 0-g simulation (water immersion).

Lower body negative pressure (LBNP) remains an important device for the generation of orthostatic stress in the space flight environment as well as a tool to measure inflight and postflight changes in orthostatic response. These applied levels of LBNP have typically not exceeded 50-60 mm Hg negative pressure. Information is incomplete as to the levels of absolute LBNP orthostatic tolerance, and the factors responsible for their variance. A better definition of the tolerance limits for males and females could be expected to aid the evaluation of lower levels of LBNP. An LBNP device was built to study absolute orthostatic tolerance; additionally, another LBNP device was constructed to permit orthostatic tolerance testing directly after a controlled water immersion period. Absolute LBNP orthostatic tolerance patterns are analyzed for a group of males and females (series I). A preliminary statement on the variations of LBNP orthostatic tolerance after limited periods of water immersion and bed rest is also provided (series II).

Male and female characteristics in vestibular testing: a step toward the selection of the best participants for space flight.

Vestibular disturbances in connection with space flight were reported by a majority of participating astronauts and cosmonauts. These include motion sickness symptoms in the first few days of the space flight, as well as standing, gait and orientation disturbances after the return to Earth. The Aerospace Medical Community has been trying to select those people that are particularly adapted to the above stresses or that can be further adapted through training programs. As the circle of selectees extends to women, the problem arises as to whether differences between men and women exist under the conditions of space flight. In seeking answers to this question we studied a group of 42 women and 44 men, who were further subdivided according to their subjective motion sickness sensitivity, as determined by a questionnaire. Using this material, 26 men and 22 women were designated as motion sickness resistant, and 18 men and 20 women were designated as nonresistant. The vestibular test battery given these test subjects consisted of caloric, rotatory, optokinetic, vestibulo-spinal and vestibulo-vegetative testing. Because of the mixed orthostatic and vestibular problems seen after space flights, we also studied the response of the vestibular apparatus during peripheral blood pooling as induced by lower body negative pressure. The collected historical and test data are analyzed in this paper with emphasis on the relationship to motion sickness tendency.