High Pressure Nervous Syndrome Research Articles

Effect of pressure on [3H]GABA release by synaptosomes isolated from cerebral cortex.

High hydrostatic pressure has been shown to produce neurological changes in humans which manifest, in part, as tremor, myoclonic jerks, electroencephalographic changes, and convulsions. This clinical pattern has been termed high-pressure nervous syndrome (HPNS). These symptoms may represent an alteration in synaptic transmission in the central nervous system with the inhibitory neural pathways being affected in particular. Since gamma-aminobutyric acid (GABA) transmission has been implicated in other seizure disorders, it was of interest to study GABAergic function at high pressure. Isolated synaptosomes were used to follow GABA release at 67.7 ATA of pressure. The major observation was a 33% depression in total [3H]GABA efflux from depolarized cerebrocortical synaptosomes at 67.7 ATA. The Ca2+-dependent component of release was found to be completely blocked during the 1st min of [3H]GABA efflux with a slow rise over the subsequent 3 min. These findings lead us to conclude that high pressure interferes with the intraterminal cascade for Ca2+-dependent release of GABA.

Influence of hyperbaric heliox environment at 31ATA on microvibration and electroencephalogram in four divers.

The simulated experiment of heliox dive to 31ATA in four subjects was periormed for one month including the pressure holding for one week. In order to study the influence of hyperbaric environment on physical condition and level of consciousness, microvibration (MV) on thenar and eyelid and electroencephalogram (EEG) on T4 and O2 were measured at various atmosphere conditions. The power spectrum of MV and EEG were calculated : The peak frequency of power spectrum and the magnitude of power spectrum at the peak frequency were evaluated. The amplitude of MV increased after compression as compared with the value at pre-compression i.e., 1ATA, and the tendency was emphasized on eyelid MV at post-compression i.e., 1ATA, whereas the peak frequency of MV did not change significantly throughout the experiment. A rerharkable hyperbaric effect was found in the evaluation of EEG peak frequency ; The lowering of the peak frequency was recognized during the process of compression, pressure holding, and decompression. As the high pressure nervous syndrome (HPNS), especially during compression, was not recognized here, MV was not used as a detector of omen of HPNS, but the hyperbaric effect on skeletal muscle was found in ballistocardiogram cornponent of MV due to the increase of the amplitude at post-compression. EEG denoted the lowering of level of consciousness during pressure holding, so that the result meant calling one's attention to the operation in hyperbaric environment of 31ATA.

Subjective signs and symptoms in divers during compression with heliox to 300 meters(31 ATA)

Four divers were compressed with He-O2 (PO2= 0.3 bar) at 25m/h to 300m(31 ATA). During the compression, all the divers answered a questionnaire and kept a personal log of their signs and symptoms including the time of onset and site of any arthralgias and fatigues. Symptoms of fatigue which include drowsiness, brain muddled and rigid or clumsy in motion appeared in all divers from 100m to 300m. The arthralgia and myalgia were deflnitely present but mild from a depth of 150m. At the same depth, the tremor appeared practically imperceptible. However, the symptom of tremor was not complained during the compression from 200m to 300m in the two divers (A and C). The nausea and dizziness associated with high pressure nervous syndrome (HPNS) were complained barely perceptible or minimal from a depth of 250m in the divers A, C and D. At the depth of 300m, these symptoms were kept on and the physical condition of the divers prevented them from working immediately. The feeling of adaptation in this environment was answered after 24h (diver D), 32h (diver A and C) and 80h (diver B) on the bottom. These results showed that there was a signiflcant interindividual variation in susceptibility to subjective signs and symptoms.

Effects of addition of nitrogen during rapid compression of baboons.

A series of dives was carried out to depths of 600 and 800 m seawater (msw) using baboons (Papio papio). Experiments were designed to study the effects of compression and the use of a He-N2-O2 gas mixture on high-pressure nervous syndrome (HPNS). When N2 was added to the He-O2 mixture at the beginning of a linear compression (200 msw/h), the symptoms associated with HPNS were still seen; in addition, the electroencephalogram (EEG) changes were more severe than those seen without N2. By use of an identical mixture, a 2-h exponential compression to 600 msw produced less severe signs of HPNS than the nonexponential profile. By use of a 2-h exponential compression to 600 msw and with addition of N2 at the end of compression, the HPNS that had been started under the He-O2 mixture decreased. Progressive addition of N2 during compression reduced the behavioral signs of HPNS without further EEG changes. These results show that the action of N2 is more complex than can be explained by a simple narcotic pressure antagonism and that the HPNS differed according to the gas mixture used.

HPNS of baboons during helium-nitrogen-oxygen slow exponential compressions.

From the results obtained with the experimental series CORASIN (fast compression with He-N2-O2), a method of compression has been developed for the baboon (Papio papio) to dive deeper than 600 m. This method utilizes an exponential compression profile with stages of 40 min every 100 m and with the introduction of N2 before each stage from 200 m onward to maintain a concentration of 5.5%. Between 0 and 800 m, this procedure did not produce myoclonus or epileptic seizures; tremor appeared beyond 400 m (578 +/- 109 m) but remained slight. If N2 was not introduced, the tremor appeared earlier (266 +/- 52 m) and became severe; between 600 and 800 m, muscular hypertonus, myoclonus, and muscular cramps occurred. The modifications of the electroencephalogram were slight; the increase in slow activity did not exceed 300% with or without N2. Beyond 800 m, the compression procedure with N2 injections revealed new phenomena. There was a general depression of EEG activity starting at 800 m; from 1,000 m and deeper, there were periods of motor disturbances (hypertonus, spasms, and shaking), palpebral clonus, and eye movements associated with peak EEG activities localized in the posterior region of the skull that sometimes evolved toward an epileptic seizure localized in this region. These symptoms differed from the classical description of high-pressure nervous syndrome, which comprises an increase in tremor followed by convulsions. These differences may perhaps be linked to our compression procedure using N2 injection, to the effect of the pressure itself, or to a combination of the two.

High pressure nervous syndrome: psychometric and clinico-electrophysiological correlations.

The high pressure nervous syndrome (h.p.n.s.) was studied in man from clinical, electrophysiological and psychometric viewpoints during a variety of simulated dives to depths deeper than 300 m (between 300 and 610 m), which used different modes of compression and different gas mixtures (Heliox, Trimix). In particular we studied tremor, myoclonia, changes in electroencephalogram and psychometric performance. Three points stemmed from these results. Some h.p.n.s. signs are present whichever technique is used, while others depend on the technique, both in intensity and in quality; so there is a syndrome due to compression, whose effects diminish, and a pressure syndrome, which persists at depth. There are differences between the susceptibility of different individuals, not only concerning h.p.n.s. as a whole, but also each symptom and its evolution at a given constant depth. There are no close correlations between the different symptoms observed.

Norwegian deep diving trials.

In 1983 NUTEC, together with two diving companies, completed two dives with 12 divers (6 in each dive) to pressures equivalent to 350 m s.w., one dive lasted for 17 d, and the other, 24 d. The purpose of the dives was to demonstrate that the diving companies were prepared for diving to 300 m depth in the North Sea. No major medical or physiological problems arose during the dives, although all divers had minor symptoms of high pressure nervous syndrome during compressions. During decompression three decompression sickness incidents occurred, which involved pain only, and all were successfully treated. All divers went through comprehensive medical physiological examinations before and after the dives. No significant changes from values measured before diving have been found in the six divers who have so far been examined after diving, except that five of them were considerably more sensitive to CO2 after the dive than before. Several problems arose in connection with the divers' breathing equipment, thermal protection and communication, which need to be improved.

Probing the limits of human deep diving.

Divers breathing compressed air are restricted to 45 m depth because of the narcotic effects of nitrogen and toxic action of oxygen at increased pressures. Substitution of oxygen-helium for compressed air has permitted divers to reach 600 m. However, at depths greater than 160 m, signs and symptoms of the high pressure nervous syndrome (h.p.n.s.) occur, with tremors, myoclonic jerking, nausea, vomiting, fatigue, somnolence, e.e.g. changes, dyspnoea, and poor sleep with nightmares. It has been the objective of this Laboratory to ameliorate the symptoms of pressure-induced h.p.n.s. by the addition of small amounts of 'narcotic' nitrogen to the oxygen-helium mixture to form the Trimix breathing gas. In 1973, comparative experiments with oxygen-helium and the same divers, during compressions in only 33 min to 219.5 m and 305 m, showed such Trimix to be effective with 10% (by volume) nitrogen. Simulated dives, termed ATLANTIS, have been made with Trimix over the last 4 years to depths in excess of 610 m for 11 days, 650 m for 4 days and 686 m for 1 day. The objectives were to determine the effects of either slow or rapid rates of compression, and either 5% or 10% (by volume) nitrogen in Heliox, on the presence of h.p.n.s. or nitrogen narcosis. Measurements were made of intellectual and psychomotor performance, electrophysiological function of the brain and reflexes, lung and cardiovascular function, including arterial gas analysis at rest and work, blood chemistry and psychiatric and psychological status. The results permit the conclusion that divers may be compressed safely to depths as great as 686 m. The technique requires a slow exponential compression over days, with frequent stages lasting 14 h or more, the use of 5-8% (by volume) nitrogen in Heliox and careful selection of the divers.

Introductory remarks to the second session

It is challenging indeed to be invited to introduce this broad-ranging session, for it encompasses virtually all levels of the effects of pressure and its antagonism by narcotics from the molecule to man. The papers will take us from the talk of Dr A. MacDonald on the reversible effects of pressure on molecules, and thereby cell structure and function, (MacDonald 1982) to Dr K. Miller and his co-workers, who will discuss the action of pressure on membranes and mammals such as mice to produce the high pressure nervous syndrome.

Ionic currents in vertebrate myelinated nerve at hyperbaric pressure.

To establish a base line for a study of anesthetic-pressure antagonism in axons, voltage-clamped nodes of Ranvier from amphibian sciatic nerve were subjected to pressures of 1-100 atm. Over the time of compression, there was usually an irreversible decrease in peak inward sodium current, but there was no change in peak outward sodium current or in the current-voltage relationship. The steady-state inactivation-voltage curve was shifted 5-15 mV in the depolarizing direction at 70-100 atm. The rate of rise of the sodium current was slowed, as was the time constant of inactivation (tau h). Increase in tau h was markedly voltage dependent, suggesting a selective effect of pressure on beta h, the rate constant governing development of the inactive state. The rate of development of steady-state outward potassium current was also decreased, without significant change in maximum current. The effects of pressure are qualitatively similar to, but different in detail from, those reported in squid axon and different in some details from the effects of cooling in this preparation. None of the effects can presently be related to the high-pressure nervous syndrome.

A new appraisal of high pressure nervous syndrome.

The principal symptoms of High Pressure Nervous Syndrome (HPNS) were described for Man in 1969. Results obtained since then, for monkeys as well as for Man, have shown that while these original observations remain valid, they must be slightly revised. Firstly, all the symptoms of HPNS do not obey the same laws. Secondly, the gravity of HPNS does not depend only on the depth attained. The symptoms depend on the gas mixture used and, for a given gas mixture at a given depth, on the rate and mode of compression. It is possible to reduce the gravity of HPNS by using a specific mode of compression. However, it should be noted that the disappearance of a given symptom due to the modification of one or several parameters of the compression, does not necessarily signify the disappearance of HPNS. Experiments are still necessary to evaluate the most significant alarm signals for each type of compression used.

Control of HPNS [high pressure nervous syndrome] in humans during rapid compression with trimix to 650 m (2132 ft.) : Bennett, P.B., R. Coggin and J. Roby, 1981. Undersea biomed. Res., 8(2):85–100

Control of HPNS [high pressure nervous syndrome] in humans during rapid compression with trimix to 650 m (2132 ft.) : Bennett, P.B., R. Coggin and J. Roby, 1981. Undersea biomed. Res., 8(2):85–100

Diazepam under hyperbaric conditions in rats.

The effect of diazepam, expressed as loss of the righting reflex, in 60 adult rats compressed with oxygen/helium to 90 ATA was compared to 18 diazepam-treated rats at 1 ATA. A marked pressure reversal of the loss of righting reflex was found. Convulsions provoked by high helium pressure were prevented by diazepam and the symptoms of High Pressure Nervous Syndrome (HPNS) were reduced.

Diving Injuries to the Inner Ear

Most of the previous literature concerning otologic problems in compressed gas environments has emphasized middle ear barotrauma. With recent increases in commercial, military, and sport diving to deeper depths, inner ear disturbances during these exposures have been noted more frequently. Studies of inner ear physiology and pathology during diving indicate that the causes and treatment of these problems differ depending upon the phase and type of diving. Humans exposed to simulated depths of up to 305 meters without barotrauma or decompression sickness develop transient, conductive hearing losses with no audiometric evidence of cochlear dysfunction. Transient vertigo and nystagmus during diving have been noted with caloric stimulation, resulting from the unequal entry of cold water into the external auditory canals, and with asymmetric middle ear pressure equilibration during ascent and descent (alternobaric vertigo). Equilibrium disturbances noted with nitrogen narcosis, oxygen toxicity, hypercarbia, or hypoxia appear primarily related to the effects of these conditions upon the central nervous system and not to specific vestibular end-organ dysfunction. Compression of humans in helium-oxygen at depths greater than 152.4 meters results in transient symptoms of tremor, dizziness, and nausea plus decrements in postural equilibrium and psychomotor performance, the high pressure nervous syndrome. Vestibular function studies during these conditions indicate that these problems are due to central dysfunction and not to vestibular end-organ dysfunction. Persistent inner ear injuries have been noted during several phases of diving: 1) Such injuries during compression (inner ear barotrauma) have been related to round window ruptures occurring with straining, or a Valsalva's maneuver during inadequate middle ear pressure equilibration. Divers who develop cochlear and/or vestibular symptoms during shallow diving in which decompression sickness is unlikely or during compression in deeper diving, should be placed on bed rest with head elevation and avoidance of maneuvers which result in increased cerebrospinal fluid and intralabyrinthine pressure. With no improvement in symptoms after 48 hours, exploratory tympanotomy and repair of a possible labyrinthine window fistula should be considered. Recompression therapy is contraindicated in these cases...

Experimentation hyperbare (110 atmospheres) chez un crustace amphipode talitridae

Males and females of the Amphipod crustacean Orchestia gammarella (Talitridae) in period of sexual activity were isolated and compressed in an experimental hyperbaric chamber at pressures between 20 and 110 ATA with oxygen-helium (heliox) mixture (PIo2 = 300 torr). Stay duration under pressure was 16 days. This stay under pressure did not induce any important disorder like a high pressure nervous syndrome except excitement during compression between 70 and 110 ATA; phenomena of shedding of skin and reproduction did not change; rate of masculinity of the lineage was not modified. Slow decompression did not bring out bends. 110 ATA pressure with heliox mixture does not appear to induce obvious deterioration neither in cellular metabolism nor in physiological functions for instance, the intricate functions of reproduction.

Effects upon the EEG of psychometric performance during deep dives in helium—Oxygen atmosphere

A study of EEG modifications and psychometric performances was performed during two dives in hyperbaric chambers with a helium—oxygen breathing mixture (pO 2 maintained at 0.4 ATA). The depths attained were 500 m for the first experiment (Sagittaire II) and 610 m for the second (Physalie VI). Four subjects were studied. EEG modifications that could be considered as high pressure nervous syndrome began at 300 m. They were characterized by an increase of slow activity (particularly theta), depression of fast activity and transformation of the waking EEG into one resembling that of stage I sleep. The psychometric tests revealed a diminution of sensorimotor performance in all subjects (10–20%). Performance in intellectual tests varied according to subject and experiment, and did not fall more than 15% below normal values. An increase in theta activity was observed in the anterior regions while the subjects performed certain psychometric tests (number ordination; symbol recognition double word; digital dexterity). This increase, which could reach 700% of the values recorded during periods of rest preceding or following the tests, appeared at 350 m and deeper. These modifications could be due either to deficits in cerebral oxygenation, to perturbed cerebral blood flow, or to alterations in energetic or metabolic processes caused by hyperbaric conditions. These alterations appeared during repetitive tasks which necessitated constant effort and attention.

Neuromuscular function at hyperbaric pressures: pressure-anesthetic interactions.

Hydrostatic pressure and anesthetic agents exert mutually antagonistic effects, including pressure reversal of anesthesia and anesthetic amelioration of the high-pressure nervous syndrome. To clarify the cellular basis for these phenomena, twitch tension and electromyogram (EMG) were monitored in the indirectly stimulated isolated rat diaphragm. Compression to 137 atm increased twitch tension without changing EMG amplitude. Partial phrenic nerve block accompanied EMG depression induced by methoxyflurane and chloroform; pressure antagonized these effects. To examine subthreshold pressure effects, calcium concentration was decreased from 2.5 to 0.5 mM. Compression to 137 atm then reversibly decreased EMG amplitude, while enhancing twitch tension. In 0.5 mM calcium, methoxyflurane and chloroform depressed EMG amplitude before blocking phrenic nerve conduction; pressure to 137 atm produced additional depression. These results suggest that pressure enhances twitch tension by acting on excitation-contraction coupling or on the contractile mechanism. They also indicate that pressure may inhibit transmission at the neuromuscular junction, and they do not support synaptic transmission as a site of pressure-anesthetic antagonism.

The compression-ordering and solubility-disordering effects of high pressure gases on phospholipid bilayers.

Abstract Inert gases at high pressure may compress and dissolve in tissue of intact organism to result in narcosis, reversal of the effects of anesthetic agents or hyperexcitability. The effects of 51 and 102 atm of helium, hydrogen, nitrogen, argon, xenon and nitrous oxide on the molecular motion of nitroxide spin-labeled phospholipid-cholesterol bilayers were measured by electron paramagnetic resonance (EPR) techniques. Immediately, application of high pressures of all gases decreased the molecular motion of the fatty acid chains of the membrane phospholipids; the magnitude of ordering was linearly related to the amount of pressure applied. The second effect was an increase in molecular motion of the fatty acid chains which appeared more slowly due to the slow gas diffusion through the column of lipid dispersion. The magnitude of disorder of the phospholipid membrane at equilibrium correlated with the known lipid solubilities of the gases in olive oil as well as with the anesthetic potency of all the gases except xenon. The environment of the spin label became less polar as the gases diffused into the bilayer. The present studies in the phospholipid model membrane show that the net effects of high pressure gases in the lipid phase consist of an initial ordering of the membrane by compression opposed by the ability of the gas molecules to diffuse and dissolve in the lipid bilayers and disorder them. It is thus suggested that the resultant perturbations of the membrane lipid fluidity by high pressure gases may subsequently be transmitted to membrane-bound protein to result in changes that may be associated, in part, with the diverse effects of anesthesia and of the high pressure nervous syndrome (HPNS) observed in deep-sea divers. The model system may be useful in developing gas mixtures which minimize HPNS.

Pressure reversal of narcosis produced by anaesthetics, narcotics and tranquillisers

THE first demonstration of pressure reversal of anaesthesia in amphibians was provided by the tadpole experiments of Johnson and Flagler1 with ethanol and ethyl carbamate. Since then the phenomenon has been studied using general anaesthetics in newts, mice and marine organisms2,3, but few of these agents have been studied in detail and the results in some cases, for example, for barbiturates4,5, are conflicting. Another aspect of the interaction of pressure and anaesthesia is the amelioration of the high pressure nervous syndrome by nitrous oxide, hydrogen or nitrogen6–8. It is not, however, known if other agents can also give ‘pressure protection’, and tadpoles provide a relatively easy model for a preliminary screening of potentially suitable drugs. We have studied both these aspects of the interaction between pressure and narcosis using intravenous, local and inhalational general anaesthetics and tranquillisers. We show that pressure reversal occurred with all our agents producing narcosis in tadpoles, whereas pressure protection does not seem to be as universal.

The high pressure nervous syndrome during a simulated oxygen-helium dive to 1500 ft

Previous simulated very deep diving experiments in which subjects have been exposed to high pressures of oxygen and helium have led to the suggestion of a “Helium Barrier” at 1200 ft due to the presence of a High Pressure Nervous Syndrome (HPNS), characterized by helium tremors, a marked increase in theta (4–8 c/sec) activity and “microsleep” involving periods of somnolence. In the present 15 day experiment two subjects were compressed to 1500 ft in an oxygen-helium environment, where they spent 10 h. During the compression, 24 h were spent at 600, 1000 and 1300 ft. and 1 h at 1100, 1200 and 1400 ft. A thorough study was made of any physiological, psychological or medical changes, with particular note being made of changes in the EEG frequencies and auditory evoked response in order to determine the aetiology of the HPNS. During each compression phase the theta activity markedly increased while the faster alpha, beta 1 and beta 2 activities decreased. These shifts continued for 6 h, even after compression had stopped, and during a further 12 h returned to much lower values. Auditory evoked potentials showed progressive depression at 1500 ft. These changes were accompanied by “helium tremors” or trembling of the hands and, in one phase of the experiment in one of the subjects, evidence of “microsleep”. It is concluded that the HPNS exists but that it may be ameliorated by slow compression, with stages of at least 24 h at interim depths to permit adaptation.