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The neural mechanisms underlying the high pressure neurologic syndrome (HPNS), which limit man's safe advance to extreme diving depths, are still unclear. This work was aimed at a better understanding of HPNS through study of brainstem auditory-evoked potentials (BAEP). BAEP were repeatedly recorded within 2 experimental chamber dives, Titan VIII (2 divers, maximum depth of 560 msw, compression time to bottom 109 h) and Titan XI (3 divers, maximum depth of 615 msw, compression time to bottom 240 h). Prolongation of the IV/V-complex occurred in 2 divers upon reaching 525 msw during Titan VIII compression and was accompanied by vestibular disturbances and amplitude increases of finger tremor. Both categories of changes--clinical signs and IV/V delay--gradually diminished during a 4-day stay at 545 msw, suggesting that they depended on excessive compression rates and insufficient acclimation time. Longer holding times at intermittent depths during Titan XI clearly reduced both HPNS symptoms and magnitude of prolongation of IV/V latencies. Wave I and wave III latency did not significantly change, pointing to a suppression of pontomesencephalic transmission. We infer that pressure suppresses synaptic transmission or triggers an increase of cortical or subcortical efferent inhibitory modulation of upper pontine and midbrain auditory afferents. Postdive controls revealed no persistent changes of BAEP measures in either the Titan VIII or XI divers.

Differences in risk of decompression sickness (DCS) that have been observed among inert gases may reflect differences in gas solubility or diffusivity or both. A higher risk gas might generate a larger volume of evolved gas during decompression, thereby increasing the probability of DCS. If this hypothesis is correct, the composition of bubbles that develop during decompression should reflect such gas differences. Unanesthetized guinea pigs were compressed to depths ranging from 250 to 350 fsw with air, He-O2 (21% O2) or one of a number of N2-He-O2 or N2-Ar-O2 mixtures (21% O2). Animals were held at depth from 15 to 60 min, then decompressed slowly (60 fsw/min) or rapidly (less than 15 s) to 5 fsw. If severe DCS developed, as judged by changes in physiologic variables, death usually occurred quickly. Gas/blood samples were then immediately withdrawn from the right atrium or the inferior vena cava, and the gas phase analyzed for He, N2, Ar, O2, and CO2 via gas chromatography. Bubbles from all dives contained 5-9% CO2, 1-4% O2, with the balance inert gas. Bubbles after N2-He-O2 dives contained substantially more N2 than He (up to 1.9 times more) compared to the dive mixture; bubbles after N2-Ar-O2 dives contained more Ar than N2 (up to 1.8 times more). For N2-He-O2 dives, the actual inert gas makeup of bubbles was dependent on the time-at-depth and the decompression profile. Results may reflect differences among He, N2, and Ar in tissue solubility/diffusivity and gas exchange rates, and support the rank order of increasing DCS risk (He less than N2 less than Ar) and rate of gas exchange (N2 less than He) observed previously during rat dives.

The increase of theta activity (4-7 Hz) in the electroencephalogram (EEG) during deep diving is commonly attributed to pathophysiologic mechanisms underlying the high pressure neurologic syndrome. The aim of this study was to clarify whether more precise cognitive aspects of the condition may be described in which theta activity occurs during a deep dive. Among 4 divers who were repeatedly examined during the GUSI 14 dive to 450 msw, 3 divers exhibited a pronounced correlation between short-term memory load, as varied by the memory set size of Sternberg's memory search task (MST), and the size of a distinct peak in the theta band of the EEG-power spectrum. The power of this peak was greatest in the fronto-central electrode position (Fz), increased dramatically during MST-performance at pressure, and failed to subside fully 1 day before surfacing. Despite the close dependency of observed theta activity on cognitive demands, no consistent correlation with performance measures (mean reaction time and errors) was found. In one diver, theta waves of similar morphology appeared in the resting EEG and increased significantly during the dive. We suggest two alternative explanations for the positive interaction of memory load and hyperbaric exposure on Fz-theta: a) Both factors induce a state of increased mental effort or selectivity of attention, known to be accompanied by frontal theta activity from normobaric studies. b) Pressure abnormally facilitates or patterns rhythmical excitations underlying theta activity that would occur naturally to a lesser extent during certain mental activities, learning, or repetitive short-term memory operations.

Four subjects were compressed to a simulated depth of 450 msw (46 bar) for 37 days in the main research chamber of the German underwater simulator diving facility at the GKSS Research Center, Geesthacht. The ambient gas was trimix. Urine was collected at 0700, 1300, and 1900 h each day for analysis of Na+, K+, volume, osmolality, and creatinine. Urine, antidiuretic hormone (ADH), and aldosterone were analyzed separately. Daily fluid, Na+, and K+ intake were analyzed throughout the dive. The aim of the investigation was to confirm the existence of a diuresis and natriuresis which had been observed in earlier saturation dives to 31 atm abs using He-O2. A significant diuresis was observed during compression despite a decrease in fluid intake. After compression the diuresis decreased somewhat but remained significantly above precompression control levels during the entire hyperbaric exposure. No significant change in fluid intake was observed. Daily Na+ and K+ excretion increased significantly during compression, which was accompanied by a significant increase in nocturnal excretion of Na+ and K+. Daily intake of Na+ and K+ decreased throughout the dive. Daily urine ADH decreased immediately upon compression and was associated with a parallel decrease in urine osmolality. In contrast, urinary aldosterone excretion exhibited no change during the dive despite the increase in Na+ and K+ excretion and decrease in Na+ intake.

During the 1980s a large new simulated underwater saturation diving system was constructed at GKSS, Geesthacht, Germany. This German Underwater Simulator (GUSI) has performed over 18 trimix (helium, 5% nitrogen, oxygen) dives with 115 divers at depths to 600 m, including 9 to 450 m or deeper for a total of 2672 man-days of saturation and 994 days of welding and other work. From October 1989, an international research program was initiated to permit scientists from other countries to carry out physiologic and medical research during these working dives. The results of the first year's program from 3 dives, GUSI 14, 16, and 17, all to 450 m, are described in this special edition of Undersea Biomedical Research. This brief paper gives the scope, design, and objectives of the program, the dive profiles, and the scientists and projects involved.

This study reports the changes in body composition measured during 6 deep saturation dives, the depths and the working hours performed during the dives, and the effects of these parameters on the energy requirements. Changes in lean body mass could be avoided if the working days amounted to 40-45% of the total dive time. Energy requirement depended not only on working days but also on the diving depth. Physical work at great depth requires a disproportional increase in the energy requirements beginning between 200 and 360 m. Under working conditions at 450 msw, energy requirements increased about 30% relative to the total energy needs under normal conditions.

Urinary vasopressin (VP), aldosterone (ALDO), osmotic substances, sodium excretion, and plasma volume were assessed in 4 healthy male divers during 2 predive control days, 2 compression days, 6 days at 46 atm abs, and 26 days of decompression with stops at 37 and 27 atm abs. At pressure the ambient gas was trimix (0.5 atm abs O2:5% N2:remainder He). All urine was collected throughout the dive. Samples were divided into daytime (0700-1900) and nighttime (1900-0700). Indocyanine green dye dilution was used to determine plasma volume at predive 1, 46, and 24 atm abs. In agreement with previous dives at 31 atm abs, there was a decrease in VP excretion during compression lasting until return to 1 atm abs (P less than 0.05). Also similar to the shallower dives at 31 atm abs, the normal diurnal pattern of VP excretion, daytime higher than nighttime (P less than 0.05), disappeared at pressure. Urine osmolality showed alterations compatible with responses to VP. In contrast to previous studies at 31 atm abs, but in agreement with a previous study at 49.5 atm abs, there was no sustained increase in urinary ALDO excretion and only a transient natriuresis during the compression phase, followed by a reduced sodium excretion. In confirmation of earlier conclusions from indirect evidence, direct measurements of plasma volume indicated a reduction of about 20% (P less than 0.05) at 46 atm abs which remained reduced after decompression to 24 atm abs.

Platelet counts were measured in 10 divers during the course of 4 experimental deep dives (450 and 600 m) and different anticoagulants were tested. The use of sodium citrate as an anticoagulant was associated with artifactual thrombocytopenia, whereas ethylenediaminetetraacetic acid proved to be satisfactory. During one of the dives (450 m) the use of fluorocarbon to remove excess dissolved inert gas before decompression of the samples was systematically tested. Mean platelet count decreased from 272,600 +/- 29,400 mm-3 (mean +/- SD) on Day 7 (450 m) to 177,700 +/- 26,400 mm-3 on Day 12 (360 m). Platelet count had recovered to 209,900 +/- 20,700 mm-3 at the time of surfacing. Mean hematocrit (expressed in percent) increased from 44.7 +/- 2.2 predive to 59.4 +/- 2.0 on Day 7 (450 m) to 40.9 +/- 2.8 at the time of surfacing. These changes were statistically significant (P less than 0.05). Platelet counts on samples that had been degassed with fluorocarbon were not different from samples that had been decompressed without degassing.

Submarine crews live in atmospheres containing variable levels of O2 and CO2. Under these conditions, significant reduction of the O2 may impair mental function during physical exertion. Therefore, psychomotor performance was measured in exercising men during Hours 26 and 57 of exposure to 21, 17, and 13% O2 in a hypobaric chamber (each gas contained 0.9% CO2, balance N1). Sea-level pressure was used except when reduced to 576 Torr at Hour 57 in 17% O2 (hypobaric-17% O2). At Hour 26 the subjects exercised at 35 and 65% of predicted VO2max They were hypoxic during exercise in 17 and 13% O2, as indicated by reduced SaO2 values (P less than 0.05). The psychomotor test (timed arithmetic) was affected by the exposure condition (P less than 0.05) but not by the work rate. At Hour 57, subjects repeated the arithmetic task at rest and at 65% of predicted VO2max. SaO2 was reduced in hypobaric-17 and 13% O2 (P less than 0.05). The math scores were affected by the work rate (P less than 0.05) but not by the exposure condition. From post-hoc analyses we conclude that 17% O2 does not impair the timed arithmetic task during submaximal exercise at normobaric pressures.

Control biochemical and hematologic data were gathered for 1017 healthy submariners who ranged in age from 19.5 to 43.5 years. Means, standard deviation, and frequency distribution are presented for 24 whole blood and serum variables and, where appropriate, for 11 urinary variables. After statistical separation of the effects of aging and length of submarine service, it has been determined that the following correlations were significant in this sample: neutrophil and leucocyte levels, serum cholesterol, and both fasting and postprandial glucose correlated positively with age; serum alkaline phosphatase levels and age correlated negatively. Age-corrected positive correlations were demonstrable between length of submarine service and both serum cholesterol content and alkaline phosphatase activity; after a loading test, glucose levels showed a negative relationship to length of submarine service. Split-sample correlation analyses verified these significant correlations, with the exception of the apparent rise in alkaline phosphatase activity with increasing length of submarine duty.

Circadian rhythms of body temperatures, pulse rate, and respiration rate were measured in 11 subjects every 4 h during certain periods on two submarine patrols. Data on systolic and diastolic blood pressure were also obtained on five crew members during the first period. All the subjects of the first patrol were on an 18-h watch schedule (6 h on, 12 h off). During the second patrol, three subjects were on an 18-h watch schedule and three were on a 24-h watch schedule. Cosinor analysis for positive (P less than 0.05) detection of rhythm demonstrated that all subjects on the 18-h watch schedule developed 18-h cycles of body temperature, pulse rate, respiration rate, and systolic and diastolic blood pressure, which were then superimposed on the persisting 24-h cycles of the same function. The three subjects on a 24-h watch schedule did not show the 18-h cycles. Moreover, additional 12-, 36-, and 48-h cycles (harmonics and subharmonics of 24-h cycles) were found in all subjects on both patrols, attesting to the disintegration of circadian cycles under these conditions. Average sleep time tended to decrease toward the end of the patrol.

Studies in nuclear submariners show that calcium excretion falls rapidly to 50% of pre-patrol levels during long patrols and remains low for many weeks after return to fresh air. This has previously been attributed to a specific effect of continuous exposure to the inevitably raised ambient CO2 levels, but other environmental factors cannot be ignored, in particular isolation from sunlight, which leads to reduced skin synthesis of vitamin D. The role of vitamin D is examined with reference to measured mean circulating blood levels of 25-hydroxyvitamin D at the beginning and end of a submarine patrol and in human exposure chamber investigations. It is concluded that although CO2 exposure has specific effects on calcium metabolism, causing a considerable reduction in urinary calcium excretion, a state of hypovitaminosis C occurs in long submarine patrols that has effects outweighing those of CO2 toward the end of patrols and afterward. The significance of this effect to submariners' health is discussed.

Medical reports from 885 Fleet Ballistic Missile (FBM) submarine patrols (7,650,000 man-days) were analyzed. The data were categorized and compared with data obtained by medical personnel from surface fleet personnel (1,215,918 man-days) during a continuous 7--8 months' deployment of surface vessels in 1973. Surface fleet personnel had a higher illness rate in the categories of respiratory, traumatic, gastrointestinal, dermal, infections, and miscellaneous illness, and a lower rate in genitourinary, systemic (including mononucleosis), cranial, and neuropsychiatric illness compared to submarine personnel. Because of improved atmosphere control, a sharp decline in the level of submarine contaminants occurred between 1965--67. Reports from the 1968--73 period showed a decrease in: 1) respiratory; 2) ear, nose, and throat; 3) gastrointestinal; 4) cardiovascular; 5) urologic; and 6) general medical illness categories; the number of general surgery, orthopedics, dental, and eye illness cases was not affected. Neurologic and psychiatric disease showed the only increases in incidence for this period. The overall decrease in illness can be attributed mainly to the fall in the incidence of respiratory disease, known to be affected by reduced air pollution, and the decline in gastrointestinal illness. This decline occurred in a period during which the incidence of both classes of illness went up in the general population, according to the Health Interview Survey published by DHEW. The improvement of atmosphere control in submarines caused a substantial reduction in contaminants (a decline in tobacco smoking also occurred in this period), which led to a decrease in incidence of illness, particularly respiratory disease. No direct causal relationship between reduction in air pollution and reduction in the incidence of disease could be proven within the framework of this study, however.

Studies of calcium and phosphorus metabolism and acid-base balance were carried out on three Fleet Ballistic Missile (FBM) submarines during prolonged exposure to elevated concentrations of CO2. The average CO2 concentration in the submarine atmosphere during patrols ranged from 0.85% to 1% CO2. In the three studies, in which 9--15 subjects participated, the urinary excretion of calcium and phosphate fell during the first three weeks to a level commensurate with a decrease in plasma calcium and increase in phosphorus. In the fourth week of one patrol, a marked increase was found in urinary calcium excretion, associated with a rise in blood PCO2 and bicarbonate. Urinary calcium excretion decreased again during the 5th to 8th week, with a secondary decrease in blood pH and plasma calcium. During the third patrol, the time course of acid-base changes corresponded well with that found during the second patrol. There was a trend toward an increase in plasma calcium between the fourth and fifth week commensurate with the transient rise in pH and bicarbonate. Plasma parathyroid and calcitonin hormone activities were measured in two patrols and no significant changes were found. Hydroxyproline excretion decreased in the three-week study and remained unchanged in the second patrol, which lasted 57 days. It is suggested that during prolonged exposure to low levels of CO2 (up to 1% CO2), calcium metabolism is controlled by the uptake and release of CO2 in the bones. The resulting phases in bone buffering, rather than renal regulation, determine acid-base balance.

A variety of vision tests have been administered to submariners over the years. The results show that the average submariner, though maintaining a normal, healthy visual system, has distant acuity somewhat below normal and manifests more myopia, esophoria, and less accommodative power than men of comparable age, as documented in the literature. The reasons for these changes are unknown but probably involve confinement; whether confinement peculiar to the submarine of the "confinement" of urban living is the more important for these changes is discussed.

An investigation into the maximum safe decompression step from oxygen nitrogen saturation to 1 bar was carried out with and without the presence of 0.02 bar carbon dioxide. The series, Islander 1, involved 13 teams of 5, fully informed, male volunteers carrying out simulated dives. One group of 6 teams carried out dives in an atmosphere of 0.4 bar oxygen, balance nitrogen (O2-N2); another group of 7 teams used an atmosphere of 0.38 bar oxygen, 0.02 bar carbon dioxide, balance nitrogen (O2-N2-CO2). The dives consisted of a 48-h stay at 1.7 or 1.8 bar to saturate the tissues, followed by decompression to 1 bar air at 0.5 bar/min. Two decompression parameters were studied; the incidence of decompression sickness (DCS) in the 24 h postdecompression, and the incidence and grade of venous gas emboli (VGE) in the first 6 h postdecompression. The grade of VGE was assessed using the Kisman-Masurel scoring system which produces a bubble grade with the subject at rest and after movement. No significant difference was found in the incidence of DCS between the two groups. Twenty subjects were decompressed from 1.7 bar using each mixture, without signs or symptoms of DCS. However, after decompression from 1.8 bar there were 2 cases of DCS in 10 subjects in the O2-N2 group and 2 cases in 15 subjects in the O2-N2-CO2 group. The incidence of detectable VGE was always lower in the O2-N2-CO2 group at both saturation pressures; at 1.7 bar the VGE incidence was lower by 40% (P less than 0.05) at rest and by 55% (P less than 0.001) after movement. At 1.8 bar the reduction was 3% (NS) at rest and 30% (NS) after movement. The results indicate that decompression from 1.8 bar to 1 bar, with or without the presence of 0.02 bar carbon dioxide, is likely to produce more than 5% DCS.

Physiological studies on hypercapnic effects carried out on 13 Polaris patrols are summarized. The average CO2 concentrations ranged from 0.7-1% CO2; CO2 was identified as the only environmental contaminant of the submarine atmosphere that has a direct effect on respiration in the concentration range found in the submarine atmosphere. A comparison has been made of physiological effects produced during 42 days of exposure to 1.5% CO2 during laboratory studies (L.S.) with those observed during 50 to 60 days of exposure to 0.7-1% CO2 on patrols (P.S.). A close similarity was found in the effects on respiration and blood electrolytes under both conditions. Respiratory minute volume was elevated by 50-63% because of increased tidal volume. The physiological dead space increased 60%. Vital capacity showed a trend toward a decrease. Studies of acid-base balance carried out during patrols demonstrated cyclic changes in blood pH and bicarbonate; pH and blood bicarbonate fell during the first 17 days of exposure, rose during the subsequent 20 days, and decreased again after 40 days. These cycles cannot be explained on the basis of known renal regulations in CO2-induced acidosis and were not found during exposure to 1.5% CO2. The hypothesis is advanced that these changes in acid-base balance are caused by cycles in CO2 uptake and release in bones. The time constants of the bond CO2 stores fit the observed length of cycles in acid-base balance. Correlation with cycles of calcium metabolism provides further support for this hypothesis. Red cell electrolytes showed similar changes under 1.5% CO2 (L.S.) and 0.7-1% CO2 (P.S.). Red cell sodium increased and potassium decreased. Moreover, red cell calcium also increased under both conditions. The significance of these red cell electrolyte changes in regard to changes in permeability and active transport remains to be clarified. An increased gastric acidity was found during patrol (exposure to 0.8-0.95% CO2). The changes observed during patrols disappeared during the recovery periods.

In a dog model of cerebral arterial gas embolism we studied the relative merits of several different treatments: air breathing at 2.8, 6, 8, and 10 bar (60, 165, 230, and 300 ft), and oxygen breathing at 2.8 bar. The study was confined to the recovery of cortical evoked potentials (CEP) while at pressure. It was confirmed that this was a very severe model; few dogs achieved full recovery and three failed to show any recovery. Injecting 0.4 ml of air into the right internal carotid artery was seen to be as effective in suppressing function in the left hemisphere as in the right. The level of recovery with compression treatment as a percentage of control was directly related to the level to which CEP was suppressed. No other physiological correlates were found with either the degree of CEP suppression or the degree of recovery. Nor was any improvement observed in the rate or maximum amount of recovery at any time out to 20 min as a result of pressures greater than 2.8 bar. Overall, no treatment surpassed oxygen at 2.8 bar.

A sizeable group of biochemical, hematologic and physiologic variables that significantly affect the prognosis for diseases of aging, especially for coronary heart disease (CHD), were studied in 1017 submariners. Skinfold thickness in these subjects was determined to be higher than in most other groups of men of similar age; the total level of body fat was within the range of high normality. Serum cholesterol levels, cigarette smoking, relative weight, and blood pressure appeared to be the factors most directly responsible for the extent of cardiovascular risk in this group of submariners. Though submariners as a group do not apparently have appreciably higher levels of CHD risk than other American men, there was a significant tendency for total risk to increase with length of submarine service as well as with age. A similar age-independent increase in serum cholesterol correlating with length of submarine service was reported earlier. Split-sample analyses support the reliability of the age-corrected correlations of CHD risk with time of submarine service. Although no attempt was made to prove a direct relationship between alcohol consumption or coffee drinking and cardiovascular risk, there were strong correlations noted. These factors, combined with serum cholesterol levels, cigarette smoking, and relative weight, deserve consideration as potentially modifiable CHD risks.

This study evaluated health risks associated with U.S. Navy submarine duty by comparing hospitalization rates of submariners with surface ship personnel. The groups were compared using age-adjusted hospitalization rates for 16 major diagnostic categories and several specific diagnoses postulated to be submarine associated. Submarine personnel did not have significantly higher hospitalization rates for any diagnostic categories nor for any of the submarine-associated illnesses. Submariner relative risk of hospital admissions was greater for a few selected diagnoses but statistical significance was not attained. Submarine personnel had lower hospitalization rates for nearly all of the diagnostic categories examined. Reasons for these lower rates may be stringent screening of submariners, higher levels of education among submariners, difficulty of evacuation from a submarine, and the healthy-worker effect. The health status of U.S. Navy personnel does not seem to be adversely affected by submarine duty.

To assess the kind and degree of attitude changes occurring during a 2-month submerged mission, two enlisted crews of one fleet ballistic missile submarine (FBM) (n = 101 each) were administered the Submarine Attitude Questionnaire before and after two 55-day submerged missions interspersed with a rehabilitation period of the same duration. Results showed that time-in-service and pay grade bore a U-shaped relationship to positive attitudes toward the service. During submergence, most attitudes became negative and then reversed polarity during rehabilitation. However, there were no cumulative effects upon attitudes during successive missions. Attitudes pertaining to the realities of the mission (for example, boredom, hazardous aspects) became more negative but recovered faster. On the other hand, attitude changes related to long-range expectancies in terms of goal achievement of the crew members were less likely to recover. Several possible explanations for these attitude changes are discussed in the context of the mission of the FBM submarine. Suggestions for preventing or alleviating untoward attitude changes during long submarine missions are also presented.

A method for studying treatment of cerebral arterial gas embolism in dogs is described. The model produces severe cortical dysfunction and cerebral blood flow deficits. The efficacy of treatment was assessed using median nerve somatosensory cortical evoked potentials (CEP), [14C]iodoantipyrene autoradiographic cerebral blood flow studies, brain water content, and various physiological parameters. A direct comparison of modified U.S. Navy Treatment Tables 6 and 6A is reported. Complete recovery of CEP was not seen after 90 min of treatment. The maximum rate of CEP recovery occurred in the first 15 min of treatment. Recovery continued out to 60 min. Thereafter, some dogs on treatment 6A showed signs of deterioration. The cerebral blood flow studies were the same in both groups and showed no sign of pathologically low levels of flow. It appeared that there was no advantage in preceding 2.8-bar (60-ft) oxygen treatments with compression to 6 bar (165 ft) on air for the treatment of arterial air embolism in this model.