[Results of the psychophysiological investigations of female test-subjects during long-term stay in pressurized chamber under the regime of therapeutic recompression].

IBMP has developed and applied protocols of therapeutic recompression of patients with delayed admission after the onset of decompression sickness or pulmonary barotraumas the occurrence of which increases among recreational divers including females. Experiment Rusalka-2004 was performed to validate a therapeutic recompression protocol with participation of female test-subjects subjected to experimental descents at air pressure of 40 and 80 m H2O (training) and of 70 m H2O (experimental) followed by 4 days at 40 to 0 m H2O in a hyperoxic (pO2 = 0.45-0.5 kgs/cm2) helium-oxygen-nitrogen atmosphere. Psychophysiological investigations during the experiment revealed only weak changes of the parameters evaluated by the well-being - activity - mood, Spilberg - Khanin, Luscher, and proof-read tests. Significant deviations in self-feeling (modified method by Dembaut - Rubinstein) and mental performance assessment (Krepelin's tables) were associated with the air pressure elevation to 40-80 m H2O both during the training and experimental descents, and symptoms of nitrogen narcosis. Based on these results, the therapeutic recompression protocol can be recommended for treatment of as males, so females.

Early and late morphological effects of experimental HPNS--animal model of psychosis?

The high pressure neurological syndrome (HPNS), a neurological condition during elevated pressure especially in deep diving, has been simulated with experimental animals. Rats were subjected to 61 bars with slow pressure increase and one or two hours constant high pressure; subsequently the pressure was released to sea level within 20 seconds--leading to immediate oxygen depletion and death of animals--or with slow decompression rates allowing survival. In all animals, brains and partly other organs were investigated morphologically. In animals sacrificed immediately, subtle changes in different brain regions were found: symmetrical occurrence of dark neurons in the hippocampus formation, cortex and brain stem, reduced expression of tyrosin hydroxylase in the substantia nigra and enhanced expression of Bax protein in some of these regions. The dark neurons were only observed after aldehyde fixation, otherwise the brains were unaltered despite ultrarapid decrease of highly elevated pressure. In animals that were allowed to survive for different time periods, some of these subtle changes were equally noted by light and electron microscopy. Furthermore, the ventricles were enlarged, the astrocytic reaction in the hippocampus increased and some signs of the destruction of the adrenal gland were visible. We conclude, that HPNS leads to minimal changes within the nervous system. The behaviour of animals during pressure was slightly altered, the weights after the experiments reduced, but no lasting sequelae were noted. Since both in human and experimental deep diving conditions signs of psychosis were reported, this HPNS model must be considered as a tentative animal model of human psychosis.

Evidence for inert gas narcosis mechanisms in the occurrence of psychotic-like episodes at pressure environment.

Psychotic-like episodes in divers exposed to high pressure have been attributed to either the high-pressure neurological syndrome, confinement in pressure chamber, the subject's personality, or the addition of nitrogen or hydrogen to the basic helium-oxygen breathing mixture used for deep diving. Alternatively, it is suggested that these disorders are in fact paroxysmal narcotic symptoms that result from the sum of the individual narcotic potencies of each inert gas in the breathing mixture. This hypothesis is tested against a variety of lipid solubility theories of narcosis. The results clearly support the hypothesis and provide new information about the cellular interactions between inert gases at raised pressure and pressure itself.

Involvement of 5-HT3 receptor in the pressure-induced increase in striatal and accumbens dopamine release and the occurrence of behavioral disorders in free-moving rats.

Rats exposed to high pressure developed locomotor and motor activity (LMA) that correlated with an increase of DA release in both the nucleus accumbens and the caudate-putamen. We investigated the effects of the 5-HT3 receptor antagonist MDL 72222 on these pressure-induced neurochemical and behavioral disorders. MDL 72222 totally blocked the pressure-induced increase in accumbens DA release and the development of LMA, whereas it only reduced the increase in striatal DA release. This suggest that both LMA and the increase of DA release in the nucleus accumbens, but not in the caudate-putamen, could specifically result from a 5-HT3 receptor activation in rats exposed to high pressure.

Lack of effect of lamotrigine against HPNS in rodent and primate models.

The neurophysiological effects of the novel anticonvulsant lamotrigine on the high pressure neurological syndrome, HPNS, were investigated in the rat and nonhuman primate Papio anubis. Rats were exposed to pressure at a rate of 3 ATA per min in a helium/oxygen environment. They were pretreated with either lamotrigine isethionate 15, 30, or 60 mg/kg IP or control vehicle. After 15 and 30 mg/kg there were no changes in onset pressures for any of the grades of tremor or myoclonus. After 60 mg/kg, tremor was much slower, at 7-9 Hz, than the 15-20 Hz seen in controls. Four baboons were exposed to pressure at 0.33 ATA per min in the same environment and treated with lamotrigine isethionate at 7.5 mg/kg/h i.v. Each animal underwent a control and a drug-treated exposure. No changes in the onset or severity of HPNS behavioural signs were observed. However, an increase in alpha wave amplitude of the EEG was almost prevented. In both species sustained myoclonic jerking occurred at pressures similar to those at which seizure activity was observed in control exposures. It is concluded that although lamotrigine is protective in several models of neuronal excitation, it is ineffective in protecting against behavioural signs associated with high atmospheric pressure.

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.

Development of anxiety symptoms during a deep diving experiment.

Six commercial divers were investigated for anxiety responses during a 29-day, open-sea world record dive at 500 meters of depth. Three of six (50%) divers developed anxiety. The authors emphasize the importance of research on personality traits as possible predictors for the development of anxiety during deep dives of exceptional depth and duration of confinement.

Interactions of the beta carboline abecarnil with the high pressure neurological syndrome in a primate model.

The neurophysiological interactions between the high pressure neurological syndrome (HPNS) and a new beta carboline, abecarnil, were studied in the non-human primate Papio anubis. Abecarnil is a partial agonist at the benzodiazepine site on the GABA/benzodiazepine receptor. Six animals were exposed on two occasions to pressures of 91 ATA in an environment of helium and oxygen. One exposure was pretreated with a total dose of abecarnil 1.0 mg/kg, the other with an equivalent volume of vehicle. Treatment with abecarnil prevented the severe signs of HPNS occurring between 51 and 91 ATA. Onset pressures of the various signs were unaffected. Some signs, e.g. myoclonus, became more frequent when abecarnil was used. A residual protective effect of abecarnil was present 4 weeks after the dose was given, active at pressures less than 71 ATA. Changes with pressure in the EEG were recorded primarily from the frontal cortex, but were also present in the parietal and occipital areas of the left cortex. Amplitude and frequency spectra were calculated and changes with pressure in the four conventional wavebands, plus two others, analysed. The most striking change was the prevention by abecarnil of the pressure-induced 100% increase in alpha wave amplitude in the frontal region. It is concluded that modulation of GABA transmission is important in controlling the expression of HPNS.

A hypothesis regarding possible interactions between the pressure-induced disorders in dopaminergic and amino-acidergic transmission.

When human divers or experimental animals are exposed to high pressure they develop the high pressure neurological syndrome (HPNS). The main symptoms include electroencephalographic changes and behavioral disturbances such as tremor, myoclonia, and hyperlocomotor activity. Recently, pressure-induced disorders in dopaminergic and amino-acidergic neurotransmission have been reported. In the present theoretical study, we review in vitro and in vivo neurochemical, electrophysiological, and pharmacobehavioral evidence concerning alterations in dopaminergic, glutamatergic, and GABAergic transmission occurring at high pressure, and their possible relationship to the symptoms of HPNS. Moreover, we also examine data concerning interactions, at normal pressure, between dopaminergic, glutamatergic, and GABAergic transmission that we suggest they could apply equally under high pressure between the pressure-induced disorders in dopaminergic and amino-acidergic transmission.

Role of dopamine receptors in the occurrence of the behavioral motor disturbances in rats exposed to high pressure.

When human divers and experimental animals are exposed to an increasing environmental pressure, they develop the high pressure neurological syndrome (HPNS) characterized by electroencephalographic changes and sleep and behavioral disturbances. In rats, behavioral disturbances essentially include hyperlocomotor activity (HLA), tremor and myoclonia. Moreover, HLA has recently been demonstrated to be linked to a pressure-induced striatal increase of dopamine (DA). In these experiments, it was proposed to investigate in rats, at the behavioral level, the role of DA receptors in the occurrence of the pressure-induced DA disturbances. DA receptor agonists were found to induce no significant changes in the development of HLA, tremor, and myoclonia. Alternatively, HLA was found to be dramatically antagonized by the use of DA receptor antagonists (SCH 23390, sulpiride, and haloperidol), while tremor and myoclonia only decreased in SCH 23390 experiments.

Exposure to high pressure may produce the 5-HT behavioral syndrome in rats.

In addition to the motor events associated with high pressure neurologic syndrome (HPNS), we have observed behavioral changes that resemble the 5-hydroxytryptamine (5-HT) syndrome in free-moving rats exposed to pressures up to 70 ATA. These include a flat body posture, head weaving, reciprocal forepaw treading, and hyperlocomotion. Such changes occur when brain 5-HT levels are raised or when 5-HT receptors are activated. We have therefore studied the behavior of rats at pressure treated either with saline or with one of the following drugs: p-chlorophenylalanine (pCPA) which depletes brain 5-HT by 85-90%, Wy 27587 which inhibits 5-HT reuptake, 5-hydroxytryptophan (5-HTP) and carbidopa which increase brain 5-HT synthesis, and quipazine which is a 5-HT receptor-agonist. After treatment, rats were individually exposed to pressure, and behavioral scores were made for 5 min every 10 ATA up to 70 ATA by an unbiased observer who was not aware of the treatment given. Analysis of all control rats indicated that only a flat body posture, forepaw treading, and hyperlocomotion were positively correlated with pressure, and these events were used in all subsequent analysis. Rats treated with pCPA with whole brain 5-HT levels reduced by 90% had scores significantly less than controls. Rats treated with Wy 27587 showed significantly increased scores. Rats treated with 5-HTP and quipazine failed to show a significant increase in scores. These results suggest that a modified form of the 5-HT syndrome occurs when rats are exposed to increased pressure, and the behavioral events seen are consistent with some activation of the 5-HT1A receptor subtype.

Neuropsychologic effects of saturation diving.

Neuropsychologic status of saturation divers was assessed before and after 300-500 msw dives (deep saturation diving--DSD group) and before and after 3.5 yr of ordinary saturation diving (saturation diving--SD group). Average baseline results showed the divers to be slightly superior to nondiving controls. Mild-to-moderate neuropsychologic changes (greater than 10% impairment) were found in measures of tremor, spatial memory, vigilance, and automatic reactivity in 20% of the divers after deep dives (DSD group). One year postdive no recovery was observed except for a vigilance test. In the SD group, 20% of the divers showed greater than 10% impairment after 3.5 yr of ordinary saturation diving. Significant reduction in autonomic reactivity was also found and there was a relationship between low autonomic reactivity before saturation diving and number of greater than 10% impairments. For the whole group (DSD + SD divers), negative correlations were found between saturation experience and results on memory and complex visuomotor tests. Years of diving from first to last examination was positively correlated with number of greater than 10% impairments and with reduction in autonomic reactivity. No similar correlations were found to dive variables after about 3 yr of air diving. The mild-to-moderate changes seen in some divers, therefore, seem to be the effects of saturation diving. Since one deep dive may cause an effect similar to the effect of 3.5 yr of ordinary saturation diving, there is reason to believe that repeated deep diving may lead to more pronounced neuropsychologic impairment.

Failure to find residual memory deficits in monkeys after repeated HPNS.

Squirrel monkeys (n = 8) were equated on learning and memory tasks before sustaining 3 separate dives in a laboratory compression chamber. Associative memory was carefully monitored 1 wk before and 3 wk immediately after each dive. The first dive was a shallow, subseizure control dive and the subsequent 2 dives were deep, seizure-inducing dives. Half of the animals were always compressed in He-O2 and half in He-N2-O2 gas, which is known to increase the depth at which tremors and seizures occur. After the control dive there was a slight (10% average) decline in memory performance, but the decline was temporary and recovery was complete by the second postdive week. There was no evidence of residual memory impairments after either of the 2 subsequent seizure-inducing dives. Although addition of nitrogen to the breathing gas significantly elevated thresholds for tremors, it had no differential effect on memory scores. These results are in agreement with studies of human divers that show either no residual impairments or transient, fully recoverable cognitive symptoms after diving.

HPNS effects among 18 divers during compression to 360 msw on heliox.

Heliox compression deeper than 16 ATA can lead to EEG changes associated with confusion and somnolence. In man the symptoms termed the high pressure neurologic syndrome (HPNS) can also include increased tremor, memory problems, dizziness, nausea, and vomiting. In a series of 3 dives at NUTEC, a compression profile developed for operational use down to 360 msw was evaluated. In each dive 6 different divers were compressed to 360 msw on heliox. Neuropsychologic and neurophysiologic testing were performed repeatedly. The HPNS testing revealed only mild effects of the compression. Only 3 divers had impairments of more than 2 SD in peripheral motor function compared to their predive average. Memory was impaired periodically in 2 divers. The same was found for perceptual speed and reasoning. Fifty percent of the divers had an increase of more than 2 SD in postural tremor, but that had minimal effect on their motor performance. Six of the 18 divers had an EEG power spectrum with both alpha band inhibition and theta increase. While the performance impairment was most marked around 240 msw, the EEG changes occurred mainly deeper than 300 msw. In only 1 of the 18 divers marked EEG changes, marked tremor increase, and marked cognitive performance impairment were observed at the same time. Although mild HPNS was observed, the divers were little impaired during the compression to 360 msw. The results confirm that using a compression profile with rates decreasing progressively with increasing depth, and with several intermediate stops, provides fit divers at depth. By using standard batteries of HPNS testing we were able to obtain evidence for the acceptability of this compression profile.

Effects of a H2-He-O2 mixture on the HPNS up to 450 msw.

A H2-He-O2 mixture with 54 to 56% hydrogen was studied with 6 subjects (professional divers) during 2 dives to 450 m. The 38-h compression was the same as that used with other types of breathing mixtures (He-O2 and He-N2-O2). The results obtained during compression and during the stay at 450 m in H2-He-O2 show that the EEG changes (increase of theta activities in the anterior regions of the skull, decrease of alpha activities) are similar to those found with other respiratory mixtures. On the other hand, the other symptoms of high pressure neurologic syndrome (HPNS) were clearly improved for the same depths. Thus, neurologic symptoms (tremor, dysmetria, myoclonia, drowsiness) are nonexistent, and the performances during psychometric tests remain similar to those of the surface. Hydrogen, with its narcotic potency, suppresses some symptoms of HPNS and seems to open new perspectives for deep diving.