High Pressure Nervous Syndrome Research Articles

A real-time R-wave detection method for wireless ambulatory ECG telemetry

Wireless ambulatory ECG telemetry has been widely used in heart rate monitoring in altered gravity conditions, evaluation of high pressure nervous syndrome (HPNS), etc. Comparing with resting ECG monitoring in the hospital, ambulatory ECG features motion artefacts caused by limb movements, including peak interference, instantaneous distortion and amplitude saltation of QRS complex. Beside, in wireless networks, packets are probably dropped because of RF range interference and complex testing environment. To solve these problems, the paper proposes a novel real-time R-wave detection method for wireless ambulatory ECG telemetry (DET). Three sequences of ambulatory ECG were measured and analysed by a custom-made bioelectricity wireless telemetry system. The overall sensitivity, positive predictivity and failed detection were 99.7%, 99.9% and 0.47%, respectively.

Modelling of noble anaesthetic gases and high hydrostatic pressure effects in lipid bilayers.

Our objective was to study molecular processes that might be responsible for inert gas narcosis and high-pressure nervous syndrome. The classical molecular dynamics trajectories (200 ns) of dioleoylphosphatidylcholine (DOPC) bilayers simulated by the Berger force field were evaluated for water and the atomic distribution of noble gases around DOPC molecules in the pressure range of 1-1000 bar and at a temperature of 310 K. Xenon and argon have been tested as model gases for general anaesthetics, and neon has been investigated for distortions that are potentially responsible for neurological tremors in hyperbaric conditions. The analysis of stacked radial pair distribution functions of DOPC headgroup atoms revealed the explicit solvation potential of the gas molecules, which correlates with their dimensions. The orientational dynamics of water molecules at the biomolecular interface should be considered as an influential factor, while excessive solvation effects appearing in the lumen of membrane-embedded ion channels could be a possible cause of inert gas narcosis. All the noble gases tested exhibit similar order parameter patterns for both DOPC acyl chains, which are opposite of the patterns found for the order parameter curve at high hydrostatic pressures in intact bilayers. This finding supports the 'critical volume' hypothesis of anaesthesia pressure reversal. The irregular lipid headgroup-water boundary observed in DOPC bilayers saturated with neon in the pressure range of 1-100 bar could be associated with the possible manifestation of neurological tremors at the atomic scale. The non-immobiliser neon also demonstrated the highest momentum impact on the normal component of the DOPC diffusion coefficient representing the monolayer undulation rate, which indicates that enhanced diffusivity rather than atomic size is the key factor.

Low susceptibility to inert gases and pressure symptoms in TREK-1-deficient mice

Nervous disorders may occur after an organism is saturated with inert gases, which may alter the lipid bilayer structure, according to their liposolubility coefficient. Increase in the nitrogen partial pressure induces a neurological syndrome called 'nitrogen narcosis'. By contrast, high pressures of helium induce epilepsy, an high-pressure nervous syndrome symptom. On the basis of an analogy with anaesthetic mechanisms, we used TREK-1 knockout mice, earlier described to volatile the anaesthetics resistance. These mice had a higher threshold of resistance to the narcotic effects of nitrogen and to the death after recurrent epileptic seizure induced by high pressure. TREK-1 channels seem to play a key role in modulating the anaesthetic potential of inert gases and in neuroprotection.

Central nervous dysfunction associated with deep-sea diving.

A group of 23 professional divers was investigated before and after dives to 300 and 350 metres of sea water. 12 divers were also studied during the actual dive. All divers presented neurological symptoms and signs during compression. Intention tremor, ataxia, motor weakness, sensory symptoms, vertigo, nausea and reduced memory were the most prominent features of the High Pressure Nervous Syndrome (HPNS). There were considerable individual differences. Neuropsychological and neurophysiological investigations performed after one dive showed no significant changes in any of the divers, while there was a clear-cut impairment in a group of 6 divers who had performed 2 dives 3 months apart. These changes indicate that there may be pressure-induced brain dysfunction which persists for a transient post-dive period. Loss of short-term memory is a prominent part of this dysfunction. Transitory neurological signs indicating focal cerebral dysfunction were found immediately post-dive in 4 divers, presumably reflecting the unmasking of pre-existing subclinical minimal CNS lesions.

Decompression sickness in the rat following a dive on trimix: recompression therapy with oxygen vs. heliox and oxygen

Trimix (a mixture of helium, nitrogen, and oxygen) has been used in deep diving to reduce the risk of high-pressure nervous syndrome during compression and the time required for decompression at the end of the dive. There is no specific recompression treatment for decompression sickness (DCS) resulting from trimix diving. Our purpose was to validate a rat model of DCS on decompression from a trimix dive and to compare recompression treatment with oxygen and heliox (helium-oxygen). Rats were exposed to trimix in a hyperbaric chamber and tested for DCS while walking in a rotating wheel. We first established the experimental model, and then studied the effect of hyperbaric treatment on DCS: either hyperbaric oxygen (HBO) (1 h, 280 kPa oxygen) or heliox-HBO (0.5 h, 405 kPa heliox 50%-50% followed by 0.5 h, 280 kPa oxygen). Exposure to trimix was conducted at 1,110 kPa for 30 min, with a decompression rate of 100 kPa/min. Death and most DCS symptoms occurred during the 30-min period of walking. In contrast to humans, no permanent disability was found in the rats. Rats with a body mass of 100-150 g suffered no DCS. The risk of DCS in rats weighing 200-350 g increased linearly with body mass. Twenty-four hours after decompression, death rate was 40% in the control animals and zero in those treated immediately with HBO. When treatment was delayed by 5 min, death rate was 25 and 20% with HBO and heliox, respectively.

Obituary

Obituary

Neuronal sensitivity to hyperoxia, hypercapnia, and inert gases at hyperbaric pressures.

As ambient pressure increases, hydrostatic compression of the central nervous system, combined with increasing levels of inspired Po2, Pco2, and N2 partial pressure, has deleterious effects on neuronal function, resulting in O2 toxicity, CO2 toxicity, N2 narcosis, and high-pressure nervous syndrome. The cellular mechanisms responsible for each disorder have been difficult to study by using classic in vitro electrophysiological methods, due to the physical barrier imposed by the sealed pressure chamber and mechanical disturbances during tissue compression. Improved chamber designs and methods have made such experiments feasible in mammalian neurons, especially at ambient pressures <5 atmospheres absolute (ATA). Here we summarize these methods, the physiologically relevant test pressures, potential research applications, and results of previous research, focusing on the significance of electrophysiological studies at <5 ATA. Intracellular recordings and tissue Po2 measurements in slices of rat brain demonstrate how to differentiate the neuronal effects of increased gas pressures from pressure per se. Examples also highlight the use of hyperoxia (<or=3 ATA O2) as a model for studying the cellular mechanisms of oxidative stress in the mammalian central nervous system.

Modulation of rat corticohippocampal synaptic activity by high pressure and extracellular calcium: single and frequency responses.

High pressure (>1.5 MPa) induces a series of disturbances of the nervous system that are generically termed high-pressure nervous syndrome (HPNS). HPNS is characterized by motor and cognitive impairments. The neocortex and the hippocampus are presumably involved in this last disorder. The medial perforant path (MPP) synapse onto the granule cells of the dentate gyrus is the main connection between these structures. We have studied high-pressure (HP) effects on single and frequency response of this synapse. Since effects of HP on various synapses were mimicked by reducing [Ca2+]o, results under these conditions were compared. Medial perforant path-evoked field excitatory postsynaptic potentials (fEPSPs) were recorded from granule cells in rat brain slices. Slices were exposed to high pressure of helium (0.1-10.1 MPa) at 30 degrees C. HP depressed single fEPSPs by 35 and 55% at 5.1 and 10.1 MPa, respectively, and increased paired-pulse facilitation (PPF) at 10- to 40-ms inter-stimulus intervals. Frequency-dependent depression (FDD) was enhanced by HP during trains of stimuli at 50 but not at 25 Hz. Depression of single fEPSPs by reduction of [Ca2+]o from 2 mM control to 1 mM at normal pressure was equivalent to the effect of 10.1 MPa at control [Ca2+]o. However, this low [Ca2+]o induced greater enhancement of PPF, and in contrast, turned FDD at 25-50 Hz into frequency-dependent potentiation. These results suggest that HP depresses single synaptic release by reducing Ca2+ entry, whereas slowing of synaptic frequency response is independent of Ca2+. These findings increase our understanding of HPNS experienced by deep divers.

Pressure (< or=4 ATA) increases membrane conductance and firing rate in the rat solitary complex.

Neuronal sensitivity to pressure, barosensitivity, is illustrated by high-pressure nervous syndrome, which manifests as increased central nervous system excitability when heliox or trimix is breathed at >15 atmospheres absolute (ATA). We have tested the hypothesis that smaller levels of pressure (<or=4 ATA) also increase neuronal excitability. The effect of hyperbaric helium, which mimics increased hydrostatic pressure, was determined on putative CO2/H+-chemoreceptor neurons in the solitary complex in rat brain stem slices by intracellular recording. Pressure stimulated firing rate in 31% of neurons (barosensitivity) and decreased input resistance. Barosensitivity was retained during synaptic blockade and was unaffected by antioxidants. Barosensitivity was distributed among CO2/H+-chemosensitive and -insensitive neurons; in CO2/H+-chemosensitive neurons, pressure did not significantly reduce neuronal chemosensitivity. We conclude that moderate pressure stimulates certain solitary complex neurons by a mechanism that possibly involves an increased cation conductance, but that does not involve free radicals. Neuronal barosensitivity to <or=4 ATA may represent a physiological adaptive response to increased pressure or a pathophysiological response that is the early manifestation of high-pressure nervous syndrome.

Opposing effects of narcotic gases and pressure on the striatal dopamine release in rats

Nitrogen–oxygen breathing mixtures, for pressures higher than 0.5 MPa, decrease the release of dopamine in the rat striatum, due to the narcotic potency of nitrogen. In contrast, high pressures of helium–oxygen breathing mixtures of more than 1–2 MPa induce an increase of the striatal dopamine release and an enhancement of motor activity, referred to as the high pressure nervous syndrome (HPNS), and attributed to the effect of pressure per se. It has been demonstrated that the effect of pressure could be antagonized by narcotic gas in a ternary mixture, but most of the narcotic gas studies measuring DA release were executed below the threshold for pressure effect. To examine the effect of narcotic gases at pressure on the rat striatal dopamine release, we have used two gases, with different narcotic potency, at sublethargic pressure, nitrogen at 3 MPa and argon at 2 MPa. In addition, to dissociate the effect of the pressure, we have used nitrous oxide at 0.1 MPa to induce narcosis at very low pressure, and helium at 8 MPa to study the effect of pressure per se. In all the narcotic conditions we have recorded a decrease of the striatal dopamine release. In contrast, helium pressure induced an increase of DA release. For the pressures used, the results suggest that the decrease of dopamine release was independent of such an effect of the pressure. However, for the same narcotic gas, the measurements of the extracellular DA performed in the striatum seem to reflect an opposing effect of pressure, since the decrease in DA release is lower with increasing pressure.

Glycine activation of human homomeric α1 glycine receptors is sensitive to pressure in the range of the high pressure nervous syndrome

The effect of hyperbaric pressure on the inhibitory glycine receptor has been investigated in voltage-clamped Xenopus oocytes microinjected with cRNA encoding the human α1 glycine receptor subunit. Heterologous expression of the human α1 subunit generated functional glycine-gated channels with properties typical of native receptors. Glycine elicited a concentration-dependent inward current which reversed polarity at −25 mV and was antagonised by nanomolar concentrations of strychnine. Concentration-response curves established for the homomeric α1 glycine receptor at 5, 10 and 15 MPa were progressively shifted to the right with respect to the concentration response curve established at atmospheric pressure (0.1 MPa). Pressure had no effect on the maximal response. The EC 50 values at 0.1, 5, 10 and 15 MPa were 190 μM, 222 μM, 338 μM and 482 μM, respectively. The results demonstrate that a receptor comprised solely of the human α-subunit is sensitive to pressure in the range that affects divers and at which the native rat spinal cord receptor is affected. This finding is discussed in the cortext of the postulated binding sites for glycine and the implications for the design of drugs to protect divers from the effects of pressure.

Effects of high pressures of various gas mixtures on rat striatal dopamine detected in vivo by voltammetry

This work was performed to study the effect of pressure of various gas breathing mixtures on dopaminergic activity in the striatum by in vivo differential pulse voltammetry using carbon multifiber electrodes chronically implanted in 23 freely moving rats. Compression (0.5 bar/min) in a helium-oxygen mixture induced an increase in striatal extracellular dopamine (DA) beginning at 10-20 bars and reaching 32% above precompression levels when arriving at 90 bars (n = 9). To demonstrate that this increase is dopaminergic, nine rats with right nigrostriatal pathway 6-hydroxydopamine lesions were compressed in the same conditions. In this case, the increase in DA did not occur in the right caudate nucleus but was recorded in the intact left caudate nucleus. To study the effects on DA increase of narcotic gases, which are known to reduce some high-pressure nervous syndrome symptoms, eight and six rats were compressed in helium-nitrogen-oxygen and hydrogen-helium-oxygen mixtures, respectively. They produced similar changes in striatal DA level in the same pressure range (23 and 20% increase, respectively, at the end of the compression). Consequently, the increase in striatal DA seems independent of the nature of the breathing mixture and seems related to the increase of pressure. The origin of this increase could be a pressure effect at the pre- or postsynaptic level.

Psychophysiological reactions in humans during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture

Six commercial divers were investigated for neurological and psychosensorimotor responses during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture containing 49% hydrogen. Results showed only moderate neurological symptoms of high-pressure nervous syndrome, whereas the narcotic effect of hydrogen was detectable, as investigated by psychosensorimotor tests. Nevertheless, the divers successfully carried out the main purpose of the operational dive, which was to prove the feasability of such diving methods by connecting specific elements of an offshore oil installation. Finally, these data support the hypothesis that hydrogen can alleviate some of the symptoms of the high-pressure nervous syndrome and can constitute a useful gas for commercial diving, as it decreases the density of the breathing mixture and therefore improves the living conditions, work, and comfort of the divers. Nevertheless, the present results underscore the relevance of research on individual susceptibility to pressure environment regardless of the composition of the breathing mixture.

Changes in respiratory muscle activity in conscious cats during experimental dives at 101 ATA.

The rationale for the present study was to test the hypothesis that increased work of breathing during experimental deep diving may lead to respiratory muscle fatigue. For this purpose, electromyograms (EMGs) of respiratory and skeletal muscles, plus electrocardiogram and electroencephalogram (EEG) derivatives, were continuously recorded in conscious cats. In each muscle group, the ratio of power in a high (H) to that in a low (L) band of EMG frequencies was computed. Direct diaphragmatic stimulation in selected animals produced a mass action potential to obtain the muscle fiber conduction velocity (MFCV). The maximal pressure was 101 ATA (1,000 msw) with a maximal duration of 72 h. Four cats breathed an He-O2 mixture and five others a ternary mixture (10% N2 in He-O2). Inspired O2 partial pressure was 350 Torr. With the He-O2 mixture, all the animals died within 2-54 h during the study at maximal depth. EEG signs of high-pressure nervous syndrome (HPNS) were present in all cats, and low-frequency (11-14 Hz) hyperbaric tremor discontinuously contaminated all EMG tracings. The H/L ratio computed from diaphragmatic and intercostal muscle EMGs increased after 12 h at 101 ATA. With the He-N2-O2 mixture, the cats survived until the end of the sojourn at 101 ATA, during which no hyperbaric tremor was detected from EMG tracings, and EEG signs of HPNS were weak or absent. From 31 ATA, the H/L ratio decreased significantly in respiratory but not in skeletal muscles; this was associated with decreased MFCV in the diaphragm after several hours at maximal depth.(ABSTRACT TRUNCATED AT 250 WORDS)

A new device for behavioral analysis on rats exposed to high pressure

The high pressure nervous syndrome (HPNS) is the term applied to the disturbances which appear when humans or animals are exposed to high pressure. The principal behavioral symptoms include locomotor activity, tremor and myoclonia. These symptoms have often been visually estimated previously, on free-moving animals, only by their onset pressure. In the present study, we report on the use of a new computerized device which enables a quantitative analysis of the behavioral symptoms of HPNS. These disturbances could be essentially dependent on the variations of pressure. This new device could also be profitably employed for other behavioral studies.

Excitatory and inhibitory amino acids involved in the high pressure nervous syndrome: Epileptic activity and hyperexcitability

Epileptic-like activities are observed in mammals exposed to ambient pressures higher than 20 atm. These symptoms are part of the so called "high pressure nervous syndrome". In the search of the cellular mechanisms of this syndrome, we examined synaptic and intrinsic pressure-induced changes in the in vitro hippocampal slice preparation in the rat. We found that pressure (80 atm) depresses the efficiency of excitatory amino acidergic and inhibitory GABA synaptic transmissions, while it increases the intrinsic excitability of the CA1 pyramidal cells and induced multiple population spikes. The changes were associated with a selective increase in the effects of NMDA andL-homocysteate, while the postsynaptic effects of GABA was unchanged. NMDA antagonists and GABA synergistic drugs antagonized the pressure-induced hyperexcitability and multiple population spikes. These results suggest that pressure would decrease transmitter release at the tested excitatory and inhibitory synapses and would facilitate NMDA postsynaptic mechanisms. Thus, changes in both NMDA and GABA processes might be involved in the development of the high pressure nervous syndrome.

Sleep disturbances in man during different compression profiles up to 62 bars in helium-oxygen mixture

Studies of sleep organization of 8 subjects were performed during 4 dives between 500 and 610 msw (51 and 62 bar) in a helium-oxygen mixture. The results of the 156 sleep records showed that sleep was disrupted from 30 bar: awake periods and stages I and II increased, stages III and IV and REM periods decreased. These disturbances, which were more intense with fast compression and recovered during decompression, can be considered as further symptoms of the high pressure nervous syndrome (HPNS).

Topographic electroencephalographic studies in a hyperbaric environment--specific reference to high pressure nervous syndrome.

Hyperbaric chamber dives at various equivalent depths below sea level, i.e. 7, 14, 19 and 31 atmosphere absolute (ATA) with helium-oxygen or helium-nitrogen-oxygen have been performed at the Japan Marine Science and Technology Center. A two-dimensional (topographic) display of the scalp EEG was used during simulated underwater experiments to determine; 1) Whether there are any characteristic EEG patterns in high pressure nervous syndrome (HPNS), 2) the relationship between the EEG changes and the compression rate, and 3) the relationship between the EEG changes and the characteristic signs and symptoms of HPNS. A two-way analysis of variance and a distribution analysis technique revealed that the topographic brain patterns depended on the diving depth and indicated the most affected brain areas during compression and decompression. Significant correlations between the diving depth and the EEG potentials were observed at different brain locations. Alpha waves showed a diffuse cortical distribution. Theta wave activity was more localized in the frontal midline region. These waves developed paroxysmally in relatively brief bursts supplanting or intermixing with normal background EEG rhythms. In our subjects, frontal midline theta activity was associated mostly with some of the characteristic features of HPNS, such as a transient episode of laughter or euphoria at depths greater than 21 ATA. An intimate correlation between frontal midline theta wave and laughter was observed. Frontal midline theta waves may be related to emotional activities induced by helium under high pressure. There were significant individual variations in susceptibility and subjective signs and symptoms. The EEG is of great value in studying man's physiological reactions in an undersea environment and also very important in selecting divers who are relatively more tolerant of a severe hyperbaric environment.

Effects of hydrostatic pressure on membrane processes. Sodium channels, calcium channels, and exocytosis.

A patch-clamp study under high hydrostatic pressure was performed by transferring cells or membrane patches into a pressure vessel (Heinemann, S. H., W. Stühmer, and F. Conti, 1987, Proceedings of the National Academy of Sciences, 84:3229-3233). Whole-cell Na currents as well as Ca currents were measured at pressures up to 40 MPa (approximately 400 atm; 1 MPa = 9.87 atm) in bovine adrenal chromaffin cells. Ca currents were found to be independent of pressure within experimental resolution. The mean amplitude and the gating kinetics of Na currents were affected by less than 20% at 10 MPa. This lack of a pronounced effect is surprising since the high-pressure nervous syndrome (HPNS), a disorder at high pressures known to result from impaired nervous transmission, manifests itself at pressures as low as 5 MPa. The results show that ion channels involved in transmission cannot be implicated in HPNS. However, when exocytosis was studied at high pressure by monitoring the cell capacitance (Neher, E., and A. Marty, 1982, Proceedings of the National Academy of Sciences, 79:6712-6716), more drastic effects were seen. The degranulation evoked by dialyzing the cell with 1 microM free Ca2+ could be slowed by a factor of 2 by application of 10 MPa. The same effect was observed for the degranulation of rat peritoneal mast cells stimulated with 40 microM of the GTP analogue GTP-gamma-S. According to these results, the process of exocytosis is the most likely site at which hydrostatic pressure can act to produce nervous disorders. Furthermore, we demonstrate that pressure can be a useful tool in the investigation of other cellular responses, since we were able to separate different steps occurring during exocytosis owing to their different activation volumes.

Effect of Pressure on the Release of Radioactive Glycine and γ‐Aminobutyric Acid from Spinal Cord Synaptosomes

Exposure to high hydrostatic pressure produces neurological changes referred to as the high-pressure nervous syndrome (HPNS). Manifestations of HPNS include tremor, EEG changes, and convulsions. These symptoms suggest an alteration in synaptic transmission, particularly with inhibitory neural pathways. Because spinal cord transmission has been implicated in HPNS, this study investigated inhibitory neurotransmitter function in the cord at high pressure. Guinea pig spinal cord synaptosome preparations were used to study the effect of compression to 67.7 atmospheres absolute on [3H]glycine and [3H]gamma-aminobutyric acid ([3H]GABA) release. Pressure was found to exert a significant suppressive effect on the depolarization-induced calcium-dependent release of glycine and GABA by these spinal cord presynaptic nerve terminals. This study suggests that decreased tonic inhibitory regulation at the level of the spinal cord contributes to the hyperexcitability observed in animals with compression to high pressure.