Physiological limitations to underwater exploration and work

Comp. Biochem. Physiol. Vol. 93A, No. 1, pp. 295-300, 1989

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PHYSIOLOGICAL LIMITATIONS TO U N D E R W A T E R EXPLORATION A N D W O R K PEa~a~ B. Bm~rErr HB 3823, Hyperbaric Center, Duke University Medical Center, Durham, NC 27710, USA (Received 14 January 1988) INTRODUCTION

Prior to 1933, diving in the Royal Navy was limited to depths of approximately 60 m using the old hardhat standard dress. In practice, however, most diving was to only 30m. In 1933, the R.N. Deep Diving Committee recommended that the maximum depth limit be increased to some 90 m (Hill et al., 1933). No further progress was then made until 1946. This was primarily due to the nitrogen of the compressed air inducing dangerous signs and symptoms of narcosis with slowing of cerebration, difficulty in assimilating facts and making rapid decisions and, at deep enough depth, stupefaction or loss of consciousness with amnesia on return to the surface. The severity increased with depth and was called nitrogen narcosis and later inert gas narcosis (Bennett, 1966, 1982a). Most navies therefore restricted routine compressed air diving to only some 45 m. T h e oxygen of the air was also a problem. As early as 1878 Paul Bert noted that increased partial pressures of oxygen induced toxicity of the lung. Pathological changes, even with 100% oxygen at 1 bar, eventually resulted in death due to destruction of capillary and alveolar endothelium, oedema, hemorrhage, arterial thickening and hyalinization, atelectasis and consolidation with severe impairment of gas exchange (Clark, 1982). In the central nervous system at only 20 m (60 It) or more, oxygen poisoning included effects such as muscle twitching leading to epileptic form seizures and with continued neuronal destruction, permanent paralysis and death (Clark, 1982). Since compressed air was therefore limited in its use for deep diving, alternatives were sought. It was Behnke, Thompson and Motley (1935), in the USA, who first concluded that compressed air at depths greater than 30m (100ft) exert a narcosis characterized by "euphoria, retardment of the higher mental processes and impaired neuromuscular coordination" which is due to the raised nitrogen partial pressure. A little later Behnke and Yarbrough (1938) noted the value of substituting the comparatively weak narcotic gas helium for nitrogen. Shortly afterwards, in the UK, Case and Haldane (1941) confirmed the American work and also set out to investigate the concomitant effects of carbon dioxide and cold. Later, in 1946, oxygen-helium trials were carried out by the Royal Navy which increased diving capaC.B~P,93/IA---T

bility to l13m (350 ft), but for a maximum of only 20 min at depth. In 1954, still with hard-hat equipment, the maximum working depth was extended to 128m (410ft) for short periods and in 1956 one record dive, breathing oxygen-helium was made by Lt. Wookey RN to 188m (600 ft) for a few minutes from the RN deep diving vessel H.M.S. Reclaim. The substitution of helium for nitrogen was based on the Meyer--Overton theory (Meyer, 1899; Overton, 1901) for anesthesia, which suggests a correlation between the affinity of an aliphatic anesthetic for lipid and its narcotic potency (Table 1). Compared with nitrogen, helium is therefore 4.26 times less narcotic than helium. On this basis, depths in excess of 305 m (1000 ft) were considered viable without signs and symptoms of narcosis and without oxygen toxicity by keeping the oxygen partial pressure at 0.5 bar or less. It was a young Swiss mathematician, Hannes Keller, who surprised everybody in 1962 by first reaching, in simulated dives in a pressure chamber, and later in the ocean, a record depth of 305 m (1000ft) while breathing helium and oxygen. He utilized a remarkably fast compression rate (2-3 bar/rain) and after only 5 min at depth an equally surprising rapid decompression to the surface in only 270 min (Keller and Buhlman, 1965) without decompression sickness--a further impediment to deep diving efforts (Buhlmann, 1982; Hempleman, 1982). However, a new and further significant limitation to man's ability to live and work in the deep oceans was about to appear and one that would be less easy to circumvent, namely the effects of the high pressure itself on the nervous system. T H E H I G H PRESSURE NERVOUS S Y N D R O M E

In 1962, deep diving trials began by the Royal Navy with the intent, over 5 years, to achieve an operational capability of 250m (800 ft) with additional research to the deeper level, 375 m (1200 It). Thus, in 1964-1965, RN divers at the RN Physiological Laboratory, Alverstoke, near Gosport in Hampshire, were first compressed to a simulated 183 m (600 ft) for 4 hr at depth and later 244m (800 ft) for 1 hr with compression rates of 30.5 m/rain (100 ft/min). During these chamber dives, unexpected decrements in performance were seen, such as 18% in arithmetic ability and 25% in fine manual dexterity

295

296

PETER B. BENNETT Table I. Correlation of narcotic potency of the inert gases, hydrogen, oxygen and carbon dioxide, with lipid solubility and other physical characteristics Gas

Molecular weight

Solubility in lipid

Temperature (~'C)

He Ne H2 N2 A Kr Xe

4 20 2 28 40 83.7 131.3

0.015 0.019 0.036 0.067 0.14 0.43 1.7

37 37.6 37 37 37 37 37

O2 CO 2

32 44

0.11 1.34

40 40

at 183 m, which was significantly worse at 244 m with a 42% decrement in arithmetic ability and 53% in manual tasks. These decrements were accompanied by unusual tremors of the hands and arms, dizziness, nausea and sometimes vomiting (Bennett, 1965, 1967; Bennett and Dossett, 1967). The condition was worse on arrival at depth with improvement over about 90 min and it appeared unlikely that divers would be able to work at 305 m (1000 ft). Bennett termed the condition "helium tremors" and postulated the causes as possibly a raised carbon dioxide tension in association with a high oxygen partial pressure and too rapid a compression. Surprisingly, as only determined in 1968, Zaltsman in Russia had published a volume in 1961 in Russian on animal and human experiments with increased pressures of helium to 131-152 m (430-500 ft) reporting rhythmic tremors of 5-8 Hz which decreased with time at pressure which he too called 'helium tremors'. Additionally, in the late 1960s Brauer et al. (1966) and Miller et al. (1967) in the USA and UK, while carrying out animal research into inert gas nacosis, showed similar signs and symptoms in rodents and suggested the cause as more likely to be the raised hydrostatic pressure p e r se and showed that at sufficiently high pressures, the animals convulsed. The condition was then termed the "High Pressure Neurological Syndrome" and later this was modified to the current "High Pressure Nervous Syndrome" or HPNS. The syndrome in man is characterized by various signs and symptoms such as dizziness, nausea, vomiting, postural and intention tremors, fatigue, somnolence, myoclonic jerking, stomach cramps, increased EEG slow wave activity (6-8 Hz, theta) and decreased fast wave activity (8-11 Hz, alpha), decrements in intellectual and psychomotor performance and poor sleep with vivid dreams or nightmares. Some divers are more susceptible than others (Hunter and Bennett, 1974). HPNS signs and symptoms may be expected, depending on the compression rate, at depths in excess of 150 m (450 ft). The success of the rapid compressions of Keller to 305 m (1000 ft) without reported HPNS caused considerable interest and speculation as to the reason. In 1968 the US Navy using the new hyperbaric research chambers at the F.G. Hall Laboratory in North Carolina confirmed the ability of man to dive with helium--oxygen to 305 m and without debilitating HPNS. This was achieved by taking a full 24 hr compression rather than the 1-2hr of Keller and

Oil-water solubility ratio

Relative narcotic potency

1.7 2.07 2.1 5.2 5.3 9.6 20.0

(least narcotic) 4.26 3.58 1.83 1 0.43 0.14 0.039 (most narcotic)

5.0 1.6

Buhlmann (Summit et al., 1971); yet the Swiss group continued with rapid compressions of only 1 hr to 305 m and only minor HPNS and even excursions with work in water at depths of 350m (ll50ft) for up to 2 hr (Buhlmann et al., 1970). Conversely, others in similar dives experienced severe and debilitating HPNS, suggesting the possibility of a physiological barrier to deep diving at around 363m (ll90ft) (Brauer, 1968) with considerable variation in personal susceptibility. The barrier concept was challenged by the author in 1970 with the first intensive physiological study of HPNS in divers. Two men, John Bevan and Peter Sharphause, were compressed with oxygen helium at 5m/min with 24hr stages at 183m (600ft), 305m (1000 ft) and 396 m (1300 ft) and 1 hr stages at 335 m (ll00ft), 366m (1200ft) and 427m (1400ft). Measurements were made of psychological efficiency, tremors, the electroencephalogram with frequency analysis, pulmonary function, EKG, blood and urine changes, etc. (Bennett and Towse, 1971a,b; Bennett and Gray, 1971; Morrison and Florio, 1971). Although tremors, nausea, myoclonic jerking and EEG changes did occur, they were comparatively mild and tended to disappear at stable depths after each compression stage. Thus, a remarkable increase of depth was achieved, and for much longer periods than ever before. The data showed that there is a considerable inter-individual response; for example, one subject showed marked tremors, the other did not. The EEG indicated for the first time, due to the on-line frequency analysis, a marked increase in theta activity, exacerbated by each compression phase. It was also clear that HPNS was a function of both the rate of compression and pressure p e r se. The faster the compression and the higher the pressure (i.e. the greater the depth), the more severe were the HPNS signs and symptoms. This study stimulated others to utilize the technique of slow exponential compressions with stages of up to 24 hr at interim depths to permit adaptation. Thus, the French made several dives including "Physalie V" with 3 d 8min to reach 520m (1706ft) for 77rain and "Physalie VI" with compression in 7 d 8 hr to 610 m (2001 ft) for 80 min and finally a 50hr stay at 610m (2001 ft) after a 10 d 21 hr compression (Rostain et al., 1978; Fructus et al., 1978). However, functional efficiency was severely limited by HPNS signs and symptoms such as tremors, fatigue and somnolence with massive increases in EEG slow wave activity, suppression of

Physiological limitations under water sleep stages 3 and 4, vivid dreams and 'out of body' experiences. Additional simulated dives to 540m (177If t) with a compression with stages of 2 d 5 hr for 2 d 12 hr at depth by the group at the RN Physiological Laboratory (Bennett, 1982b) and to 549 m (1800 ft) with a 3--4 day compression with stages and 4 days at maximum depth by the US Navy (Spaur, 1980) resulted, in both cases, in severe HPNS. There were marked tremors, dizziness, nausea, vomiting and fatigue. In the American dive, anorexia with an 8% loss of body weight occurred and stomach cramps, diarrhoea, myoclonic jerking, dyspnea and nightmares and there was a wide individual susceptibility. During the 1970's, various methods had been utilized to minimize signs and symptoms of HPNS. These included selection of the divers and a slow exponential rate of compression with stages to permit adaptation (Bennett, 1975, 1980). While this was effective in selected subjects to some 457 m (1500 ft) the HPNS at greater depths often remained too debilitating to allow the divers to be able to work or for diver safety. Another solution was required to control the HPNS. TRIMIX

While the author had been very active in study of the HPNS phenomenon and its prevention, he also had continued his interest in inert gas narcosis and its mechanisms. Thus, in the laboratories of Alec Bangham, FRS, Bennett et al. (1967) were examining the effects of raised pressures of gases on phospholipid model membranes and micelles. They noted that inert gases, such as nitrogen and argon and also carbon dioxide and oxygen, induce a fall in surface tension, implying an expansion of the monolayer, whereas helium and neon induced an opposite effect, an increase in surface tension, implying a constriction of the monolayer (Fig. 1). In 1950, Johnson and Flagler made an important observation. Tadpoles, on application of ethyl alcohol, would fall unconscious to the bottom of a tank of water but application of 150 atm hydrostatic pressure returned the tadpoles apparently to normal. This pressure reversal of narcosis has since been used Pressure of Gos

+

He + I

¢1h

O

COz Fig. 1. The effect of increased pressures of inert gases, oxygen and carbon dioxide on surface tension of an egg phospholipid rnonolayer. Narcotic gases such as nitrogen, argon and carbon dioxide cause a fall in'tension, whereas helium (and neon) causes an increase in tension (Bennett et al., 1967).

297

as an important key to understanding anesthesia mechanisms, leading later to the so-called 'critical volume theory' (Miller et al., 1973; Miller, 1974). That this phenomenon was possible also in animals was shown in mice by Lever et al. (1971a), who also suggested (Lever et al., 1971b) that 0.4% expansion of a membrane was required to effect narcosis or anesthesia and 0.4% contraction of the membrane to cause the hyperexcitability induced by pressure. These findings stimulated the author to try to control HPNS by using the reverse phenomenon and added nitrogen to the helium in sufficient quantities to reverse the pressure effects back to normal. The gas mixture used was called T R I M I X and consisted mostly of helium, a little nitrogen and 0.5 bar oxygen (Bennett et al., 1974). Early studies with T R I M I X involved rapid compression of about 10m/min to 219m (720ft) and 305m (1000ft) with nitrogen at 25% and 18%, respectively. While the tremors and nausea of HPNS were prevented, it was at the cost of euphoria and other signs and symptoms of narcosis. Therefore, a mathematical model was developed based on the Gibbs adsorption equation (Simon et al., 1975) which would give the correct nitrogen percentage to prevent either HPNS or nitrogen narcosis. The following assumptions were made: (a) Anesthetic molecules act at non-specific sites in membrane with the same oil-water partition coefficient as olive oil. (b) The gases obey Henry's Law at all pressures. (c) Helium compresses membranes whereas nitrogen and oxygen expand them. (d) The condition for elimination of HPNS and nitrogen narcosis is that the membrane area should remain constant at the pressure reached. Studies were then made of five divers exponentially compressed with three brief stages to 305 m (1000 ft) in a uniquely fast 33min while breathing 10% nitrogen in helium-oxygen (or T R I M I X 10). There were no tremors, nausea, EEG changes or significant decrements in ability and underwater work was carried out for 44 min in 56°F water by a diver who reported mild euphoria (Bennett et al., 1975). About the same time a comparison was made between 4.5% or 9% nitrogen in helium-oxygen with slower compression to 305 m (Charpy et al., 1976; Rostain, 1976). This suggested that the lower percentage ameliorated HPNS with the least narcosis effects. ANIMAL STUDIES

In parallel with the above human studies, the author conducted much animal research which will not be considered in this paper but provided further insight into the role of temperature (Cromer et al., 1976), cerebellar and EEG effects (Kaufmann et al., 1977, 1978), and effect of compression rate (Cromer et al., 1977; Cromer and Bennett, 1977) on the HPNS. In addition, basic research was carried out into HPNS mechanisms and the role of T R I M I X protection (Shrivastav et al., 1978; Cromer et al., 1979; Parmentier et al., 1979; Kaufmann et al., 1979; Simon and Bennett, 1980; Parmentier and Bennett, 1980; Parmentier et al., 1980; Bennett et al., 1980; Parmentier et al., 1981; Kaufmann et al., 1981). With the earlier human diving work, the stage was now set

298

PETER B. BENNETT

for a major extension of man's ability to dive deep in the oceans.

Table 2. D u k e / G U S I Compression Profile to 600 m with Trimix 5 (N 2 5%/0.5 bar O2/He rest) Travel 0 m - 180 m = 5 m / m i n (36 min) Stop at 180m = 2 h r

THE ATLANTIS TRIMIX DIVES

In order to investigate the value of T R I M I X at depths greater than 305 m, the author organized at the F.G. Hall Laboratory, Duke Medical Center in the USA, a series of four very deep dives named the Atlantis project which not only reached the amazing depth of 686 m (2250 ft) but also provided a unique body of data on the neurological, psychological, pulmonary and hematologic effects of such exposures. The dives utilized either 5% nitrogen in helium--oxygen or 10% and either a rapid exponential compression with adaptation stages or a rate twice as slow as the former compression. Seven divers were utilized, three of whom were involved with more than one dive. It is not possible to review the large amount of data obtained from this multidive, multi-year study between 1979 and 1982 in this limited space and which is published elsewhere (Bennett et al., 1981; Bennett et al., 1982; Salzano et al., 1981; Andersen et al., 1982; Harris and Bennett, 1983; Simpson et al., 1983; Harris and Bennett, 1984; Stoudemire et al., 1984; Bennett and McLeod, 1984; Parmentier et al., 1985). However, it may be seen from Fig. 2 that the best performance of the divers, with minimal or no HPNS, was seen with a slow exponential compression rate with stages for adaptation. Although the deepest dive during Atlantis III to 686 m, in fact, utilized 10% nitrogen in heliox with excellent control of HPNS, there was evidence of the narcotic effects of nitrogen. In Atlantis IV to 650 m the nitrogen was therefore dropped to only 5% and with the slow compression rate used for Atlantis IV. This proved the most effective combination for control of adverse signs and symptoms of HPNS and the most effective performance capability to depths of 650 m (Fig. 2).

Travel 180 m - 240 m = 3 m / m i n (20 min) Stop at 240 m = 6 hr Travel 240 m - 300 m = 1.5 m/min (40 min) Stop at 300 m = 2 hr Travel 300 m - 350 m = 0.5 m/min (1 hr 40 min) Stop at 3 5 0 m = 9 hr Travel 350 m - 400 m = 0.25 m/min (3 hr 20 min) Stop at 400 m = 2 hr Travel 400 m - 430 m = 0.125 m/min (4 hr) Stop at 430 m = 2 hr Travel 430 m - 460 m = 0.125 m/min (4 hr) Stop at 4 6 0 m = 12hr Travel 460 m - 490 m = 0.100 m/min (5 hr) Stop at 490 m = 2 hr Travel 490 m - 520 m = 0.100 m/min (6 hr 40 rain) Stop at 5 2 0 m = 13hr Travel 520 m - 550 m = 0.075 m/min (6 hr 40 rain) Stop at 5 5 0 m = 13hr Travel 550 m - 575 m = 0.05 m/min (8 hr 20 min) Stop at 575 m = 16 hr Travel 575 m - 600 m = 0.05 m / m i n (8 hr 20 min)

Final endorsement of the value of T R I M I X 5 and all that had been learned from the Atlantis dives was made during an extensive series of over 15 deep T R I M I X 5 dives by 13 divers, including 10 dives to over 300 m and one to 600 m, in a joint study by the author and the German staff at the new German Underwater Simulator (GUSI) near Hamburg (Bennett et al., 1987). The compression profile utilized was a direct development of that used for Atlantis IV (Table 2). Starting in 1983 and continuing to 1986, a series of dives was then planned to gradually work deeper toward 600m and show that divers could not only dive this deep without HPNS but could

COMPARISON FOR ATLANTIS SERIES-ADDITION TEST ofler4 doys ot depth

505m

400m

460m

560/ 610/ 5 7 0 m 600m 650m i86m 460m 650m

-30% -40% - 50%, -60%'

Illllrllll Allonlis Z .5% N2 fosl Compression [ ~

AIIonlis ~ I0% N2 fosl Compression

W///.,~J Allonlis Ill I0% N2 slow Compression ~:~

AtlontisKr 5% N2 slow Compression

Fig. 2. Results of an arithmetic test expressed a s m e a n percentage decrement from three divers on arrival at various depths during Atlantis I, II, III and IV. The adverse HPNS effects of fast compression are shown, as is the advantage of 5% nitrogen in helium-oxygen compared to 10% nitrogen in helium-oxygen (Bennett and McLeod, 1984).

Physiological limitations under water work effectively at welding or other underwater tasks without deleterious effects. The results indicated little or no HPNS during compression. The divers were fit on arrival and functionally normal with no tremors, nausea or undue fatigue. Only one of the tests in the performance battery showed any significant decrement at 500 and 600 m, namely that of perception speed, memory and calculation. However, the divers did not seem to find difficulty with their work. The EEG was remarkably free of slow theta wave activity increases but there was a definite reduction in the standard alpha activity. There was a diuresis, naturesis and loss of body weight, especially at the 500 and 600 m depths. Post dive, the divers showed the usual cardiorespiratory deconditioning and weakness which may be due to the confinement, lack of sunshine and exercise etc. The results indicated that TRIMIX 5 is a most effective method combined with a suitable exponential compression rate with adaptation stages. However, performance efficiency can be expected to fall off as one approaches 600 m. This may be due to the 5% nitrogen but, if so, it is the price to be paid for control of the HPNS which is likely to be much more incapacitating. Extensive training may be helpful. These dives form a prominent milestone of the research of the last 50 years seeking the limits to man's ability to live and work at remarkably high pressures, deep under the ocean. The research has advanced depth limits from 90 m in 1933 to 686 m in 1981 and has provided a unique and valuable body of physiological and medical data of life at such high pressures. How much deeper can man survive or do useful work? Whales can dive to 1000 m apparently without neurological problems, and mice about the same, before HPNS or convulsions occur. The use of ketamine instead of N 2 in TRIMIX will permit rats to reach nearly 2000m before convulsions occur (Halsey, 1982). That man will therefore dive deeper than 686 m in the next decade or so is virtually certain but the constraints applied by pressure will be increasingly difficult, not the least of which is the over one month of decompression required to bring the diver back to the surface.

REFERENCES

Andersen J., Bennett P. B., Carlyle R. F. and Garrard M. P. (1982) Thyroid hormone metabolism in men during simulated saturation dives to a maximum depth of 686 msw (69.6 bar). J. Physiol., Lend. 328, 47-48. Bennett P. B. (1965) Psychometric impairment in men breathing oxygen-helium at increased pressures. Medical Research Council, R.N. Personnel Research Committee, Underwater Physiology Sub Committee Report 251. Bennett P. B. (1966) The Aetiology of Compressed Air Intoxication and Inert Gas Narcosis, pp. 1-116. Pergamon Press, Oxford. Bennett P. B. (1967) Performance impairment in deep diving due to nitrogen, helium, neon and oxygen. In Underwater Physiology (Edited by Lambertsen C. J.), pp. 327-340. Williams and Wilkins, Baltimore. Bennett P. B. (1975) A strategy for future diving. In The Strategy for Future Diving to Depths Greater than lO00ft (Edited by Halsey M. J., Settle W. and Smith E.),

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Publ. No. 6-15-75, pp. 71-76. Undersea Medical Society, Bethesda. Bennett P. B. (1980) Potential methods to prevent the HPNS in human deep diving. In Techniquesfor Diving Deeper than 150Oft (Edited by Halsey M. J.), Publ. No. 40, pp. 36--47. Undersea Medical Society, Bethesda. Bennett P. B. (1982a) Inert gas narcosis. In The Physiology and Medicine of Diving (Edited by Bennett P. B. and Elliott D. H.), pp. 239-261. Bailliere Tyndall, London. Bennett P. B. (1982b) The high pressure nervous syndrome in man. In The Physiology and Medicine of Diving (Edited by Bennett P. B. and Elliott D. H.), pp. 262-296. Bailliere Tyndall, London. Bennett P. B. and Dossett A. N. (1967) Undesirable effects of oxygen-helium breathing at great depths. Medical Research Council, R.N. Personnel Research Committee. Underwater Physiology Sub-Committee Report No. 260. Bennett P. B. and Gray S. P. (1971) Changes in human urine and blood chemistry during a simulated oxygen-helium dive to 1500ft. Aerospace Med. 42, 868-874. Bennett P. B. and Towse E. J. (1971a) The High Pressure Nervous Syndrome during a simulated oxygen-helium dive at 1500ft. Electroenceph. clin. Neurophysiol. 31, 383-393. Bennett P. B. and Towse E. J. (1971b) Performance efficiency of men breathing oxygen-helium at depths between 100 ft and 1500ft. Aerospace IVied. 42, 1147-1156.

Bennett P. B. and McLeod M. (1984) Probing the limits of human deep diving. In Proceedings Royal Society meeting, Diving and Life at High Pressures (Edited by Paten W. D. M., Elliott D. H. and Smith E. B.), pp. 43-45. The Royal Society, London. Bennett P. B., Blenkarn G. D., Roby J. and Younghlood D. (1974) Suppression of the high pressure nervous syndrome in human deep dives by He-N2-Ov Undersea Biomed. Res. 1, 221-237. Bennett P. B., Roby J., Simon S. and Youngblood D. (1975) Optimal use of nitrogen to suppress the high pressure nervous syndrome. Aviat. Space Environ. Med. 46, 37-40. Bennett P. B., Leventhal B. L., Coggin R., Roby L. and Racanska L. (1980) Lithium effects: protection against nitrogen narcosis and potentiation of HPNS. Undersea Biomed. Res. 7, 11-16. Bennett P. B., Papahadjopoulos D. and Bangham A. D. (1967) The effect of raised pressures of inert gases on phospholipid model membranes. Life Sci. 6, 2527-2533. Bennett P. B., Coggin R. and Roby J. (1981) Control of HPNS in humans during rapid compression with trimix to 2132 ft (650m). Undersea Biomed. Res. 8, 85-100. Bennett P. B., Coggin R. and McLeod M. (1982) Effect of compression rate on use of trimix to ameliorate HPNS in man to 686 m. Undersea Biomed. Res. 9, 335-351. Bennett P. B., Vann R., Schafstall H. G., SchnegelsbergW. and Holthaus J. (1987) Control of HPNS with TRIMIX 5 (5% N2/He/O2) to 600m. In Proceedings 2nd International GUSI Symposium, Underwater Technology (Edited by Schafstall H. G., Schultheis G. F. and Seeliger D.), Voi. 4, pp. 1-13. GKSS Forschungszentrum, Geesthaeht/Hamburg. Brauer R. W. (1968) Seeking man's depth level. Ocean Ind. 3, 28-33. Buhlmann A. A. 0975) Decompression Theory. In The Physiology and Medicine of Diving (Edited by Bennett P. B. and Elliott D. H.), pp. 348-365. Bailliere Tyndall, London. Buhlmann A. A., Matthys H., Overrath G., Bennett P. B., Elliott D. H. and Gray S. P. (1970) Saturation exposures of 31 atm in an oxygen-helium atmosphere with excursions to 36 atm. Aerospace Med. 41, 394-402. Case E. M. and Haldane J. B. S. (1941) Human physiology under high pressure. J. Hyg. 41, 225-249. Clark J. M. (1982) Oxygen Toxicity. In The Physiology and

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Medicine of Diving (Edited by Bennett P. B. and Elliott D. H.), pp. 200-238. Bailliere Tyndall, London. Cromer J. A. and Bennett P. B. (1977) Studies of temperature, rate of compression and "trimix" on the high pressure nervous syndrome convulsion threshold in the rat. Med. Aeronaut et. spaciale. Med. Subaquatique et Hyperbare 16, 263-265. Cromer J. A., Hunter W. L. and Bennett P. B. (1976) Alteration of high pressure nervous syndrome in rats by alteration of colonic temperature. Undersea Biomed. Res. 8, 139-150. Cromer J. A., Hunter W. L. and Bennett P. B. (1977) Effect of compression rate of HPNS convulsion threshold in the euthermic rat. Undersea Biomed. Res. 4, 403-408. Cromer J. A., Bennett P. B., Hunter W. L. and Zinn D. (1979) Effect of helium/nitrogen/oxygen (Trimix) on the HPNS convulsion threshold in the rat. Undersea Biomed. Res. 6, 367-377. Fructus X. and Rostain J. C. HPNS. A clinical study of 30 cases. In Proc. 4th Symposium Underwater Physiology (Edited by Shilling C. W. and Beckett M. W.), pp. 3-8. Fed. Amer. Soc. Exper. Biol, Washington DC. Halsey M. J. (1982) Effects of high pressure on the central nervous system. Physiol. Rev. 62, 1241-1377. Harris D. J. and Bennett P. B. (1983) Force and duration of muscle twitch contractions in man at pressures up to 70 bar. J. appl. Physiol. 54, 1209-1215. Harris D. J. and Bennett P. B. (1984) Soleus H-reflex studies in man at 40-70 bar in He-O2-N 2 (Trimix). Undersea Biomed. Res. 11, 49-64. Hempleman H. V. (1982) History of evolution of decompression procedures. In The Physiology and Medicine oJ Diving (Edited by Bennett P. B. and Elliott D. H.), pp. 319-351. Bailliere Tyndall, London. Hill L., Davies R. H., Selby R. P., Pridham A. and Malone A. E. (1933) Deep diving and ordinary diving. Report of a committee appointed by the British Admiralty, London. Hunter W. L. and Bennett P. B. (1974) The causes, mechanisms and prevention of the high pressure nervous syndrome. Undersea Biomed. Res. 1, 1-28. Kaufmann P. G., Bennett P. B. and Farmer J. C. (1977) CerebeUar and cerebral electroencephalogram during the High Pressure Nervous Syndrome. Undersea Biomed. Res. 4, 391-402. Kaufmann P. G., Bennett P. B. and Farmer J. C. (1978) Effects of cerebellar ablation on the high pressure nervous syndrome. Undersea Biomed. Res. 5, 1-8. Kaufmann P. G., Bennett P. B. and Hempel F. G. (1981) Enhancement of cortical evoked potentials by high atmospheric pressures of helium. Brain Res. Bull, 7, 379-384. Kaufmann P. G., Finely C. C., Bennett P. B. and Farmer J. C. (1979) Spinal cord seizures elicited by high pressures of helium. Electroenceph. clin. Neurophysiol. 47, 31-40. Keller H. and Buhlmann A. A. (1965) Deep diving and short decompression by breathing mixed gases. J. appl. Physiol. 20, 1267-1270. Lever M. J., Miller K. W., Paton W. D. M. and Smith E. B. (1971a) Pressure reversal of anesthesia. Nature 231, 371-386. Lever M. J., Miller K. W., Paton W. D. M., Street W. B. and Smith E. B. (1971 b) Effects of hydrostatic pressure on mammals. In Proceedings 4th Symposium Underwater Physiology (Edited by Lambertsen C. J.), pp. 101-108. Academic Press, London. Meyer H. H. (1899) Theoris der alcohol narkose. Arch. Exp. Path. Pharmak. 42, 109-119.

Miller K. W. (1974) Inert gas narcosis, the high pressure neurological syndrome and the critical volume hypothesis. Science 185, 867-869. Miller K., Paton W. D. M., Smith R. A. and Smith E. M. (1973) The pressure reversal of general anesthesia and the critical volume hypothesis. Molec. Pharmacol. 9, 131-143. Morrison J. B. and Florio J. T. (1971) Respiratory function during a simulated dive to 1500 ft. J. appl. Physiol. 30, 724-732. Overton E. (1901) Studien uber die Narkose. Fischer, Jena. Parmentier J. L. and Bennett P. B. (1980) Hydrostatic pressure does not antagonize hatothane effects on single neurons of Aplysia californica. Anesthesiology 53, 9-14. Parmentier J. L., Shrivastav B. B., Bennett P. B. and Wilson K. M. (1979) Effect of interaction of volatile anesthetics and high hydrostatic pressure on central neurons. Undersea Biomed. Res. 6, 75-91. Parmentier J. L., Shirvastav B. B. and Bennett P. B. (1981) Hydrostatic pressure and anesthetics reduce synaptic efficiency of transmitter release. Undersea Biomed. Res. 8, 175-183. Parmentier J. L., Harris D. J. and Bennett P. B. (1985) Central and peripheral causes of hyper-reflexia in humans breathing 5% trimix at 650m. J. appl. Physiol. 58, 1239-1245. Rostain J. C. and Naquet R. (1978) Human physiological data obtained from two simulated heliox dives to a depth of 610 m. In Proc. 4th Symposium Underwater Physiology (Edited by Shilling C. W. and Beckett M. W.), pp. 9-t9. Fed. Amer. Soc. Exper. Biol., Washington DC. Salzano J. V., Stolp B. W., Moon R. E. and Camporesi E. M. (1981) Exercise at 47 and 66 ATA. In Underwater Physiology VII. Proceedings of the Seventh Symposium on Underwater Physiology (Edited by Bachrach A. J. and Matzen M. M.), pp. 181-196. Undersea Medical Society, Bethesda. Shrivastav B. B., Parmentier J. L. and Bennett P. B. (1978) Pressure reversal of ketamine anesthesia. Undersea Bioreed. Res. 5, 49-50. Simon S. A. and Bennett P. B. (1980) Membrane thermodynamics and anesthesia mechanisms. In Molecular Mechanisms of Anesthesia (Edited by Fink R.), pp. 305-319. Raven Press, Seattle. Simon S., Katz Y. and Bennett P. B. (1975) Calculation of the percentage of a narcotic gas to permit abolition of the high pressure nervous syndrome. Undersea Biomed. Res. 2, 299-303, Simpson D. M., Harris D. J. and Bennett P. B. (1983) Latency changes in the human somatosensory evoked potential at extreme depths. Undersea Biomed. Res. 10, 107-114. Spaur W. (1980) Recent US Navy experience in very deep saturation diving. In Techniques for Diving Deeper than 150Oft (Edited by Halsey M. J.), pp. 62~6. Undersea Medical Society, Bethesda. Stoudemire A., Miller T., Schmitt F., Logue P., Shelton D. L., Latson G. and Bennett P. B. (1984) Development of an organic affective syndrome during a hyperbaric diving experiment. Am. J. Psychiat. 141, 1251-1254. Summit J. K., Kelly J. S., Herron J. M. and Saltzanan H. A. (1971) 1000ft helium saturation exposure. In Underwater Physiology (Edited by Lambertsen C. J.), pp. 519-527. Academic Press, New York. Zaltsman G. L. (1968) Hyperbaric Epilepsy and Narcosis. Neurophysiological Studies, pp. 1-265. USSR Academy of Sciences, Leningrad.