Dopamine/BDNF loss underscores narcosis cognitive impairment in divers: a proof of concept in a dry condition.

PURPOSE: Divers can experience cognitive impairment due to inert gas narcosis (IGN) at depth. Brain-derived neurotrophic factor (BDNF) rules neuronal connectivity/metabolism to maintain cognitive function and protect tissues against oxidative stress (OxS). Dopamine and glutamate enhance BDNF bioavailability. Thus, we hypothesized that lower circulating BDNF levels (via lessened dopamine and/or glutamate release) underpin IGN in divers, while testing if BDNF loss is associated with increased OxS. METHODS: To mimic IGN, we administered a deep narcosis test via a dry dive test (DDT) at 48 msw in a multiplace hyperbaric chamber to six well-trained divers. We collected: (1) saliva samples before DDT (T0), 25 msw (descending, T1), 48 msw (depth, T2), 25 msw (ascending, T3), 10 min after decompression (T4) to dopamine and/or reactive oxygen species (ROS) levels; (2) blood and urine samples at T0 and T4 for OxS too. We administered cognitive tests at T0, T2, and re-evaluated the divers at T4. RESULTS: At 48 msw, all subjects experienced IGN, as revealed by the cognitive test failure. Dopamine and total antioxidant capacity (TAC) reached a nadir at T2 when ROS emission was maximal. At decompression (T4), a marked drop of BDNF/glutamate content was evidenced, coinciding with a persisting decline in dopamine and cognitive capacity. CONCLUSIONS: Divers encounter IGN at - 48 msw, exhibiting a marked loss in circulating dopamine levels, likely accounting for BDNF-dependent impairment of mental capacity and heightened OxS. The decline in dopamine and BDNF appears to persist at decompression; thus, boosting dopamine/BDNF signaling via pharmacological or other intervention types might attenuate IGN in deep dives.

Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Amyotrophic Lateral Sclerosis in a Patient Developing Carbon Dioxide Narcosis.

We report a rare case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with amyotrophic lateral sclerosis (ALS). A 69-year-old man was admitted to our hospital with sustained hyponatremia. Hyposmolality with elevated urinary osmolality and sodium excretion was observed, which indicated SIADH. The treatment for SIADH was challenging; the patient developed carbon dioxide narcosis, which led to the diagnosis of ALS. After the initiation of noninvasive positive-pressure ventilation, the patient's serum sodium concentration normalized and became stable. Thus, ALS should be recognized as a possible cause of SIADH in the clinical setting.

Nitrogen narcosis and tactile shape memory in low visibility.

OBJECTIVE: Commercial diving often occurs in low visibility, where divers are reliant on their tactile senses. This study examined the effect of nitrogen narcosis on tactile memory for shapes as well as the influence of psychological and biographical factors on this relationship. METHOD: This crossover study tested 139 commercial divers in a dry hyperbaric chamber at 101.325 and 607.95 kPa (1 and 6 atmospheres absolute/atm abs). Divers memorized shapes while blindfolded, using their tactile senses only. Delayed recall was measured at the surface after each dive. Psychological and biographical data were also collected. RESULTS: A significant effect of hyperbaric pressure on tactile memory was demonstrated, and a further effect of sequence of testing found. Thus, divers' delayed shape recall deteriorated by 8% after learning material at depth, compared to learning on the surface. There were also significant but small effects of psychological and biographical markers on tactile memory performance, with lower trait anxiety associated with better recall, and lower education associated with poorer recall. CONCLUSION: The findings emphasize the importance of utilizing other forms of recording of events or objects at depth, particularly in conditions of low visibility during deeper diving, to aid memory encoding and subsequent recall at the surface.

Alterations in nigral NMDA and GABAA receptor control of the striatal dopamine level after repetitive exposures to nitrogen narcosis.

Nitrogen pressure exposure in rats results in decreased dopamine (DA) release at the striatal terminals of the substantia nigra pars compacta (SNc) dopaminergic neurons, demonstrating the narcotic potency of nitrogen. This effect is attributed to decreased excitatory and increased inhibitory inputs to dopaminergic neurons, involving a change in NMDA and GABA(A) receptor function. We investigated whether repetitive exposures to nitrogen modify the excitatory and inhibitory control of the dopaminergic nigro-striatal pathway. We used voltammetry to measure dopamine levels in freely-moving rats, implanted with dopamine-sensitive electrodes in the striatum. NMDA/GABA(A) receptor agonists (NMDA/muscimol) and antagonists (AP7/gabazine) were administered through a guide-cannula into the SNc, and their effects on striatal dopamine levels were measured under normobaric conditions, before and after five repetitive exposures to 1 MPa nitrogen. NMDA-mediated dopamine release was greater following repetitive exposures, AP7-mediated inhibition of glutamatergic input was blocked, suggesting that NMDA receptor sensitivity was increased and glutamate release reduced. Muscimol did not modify dopamine levels following repetitive exposures, whereas the effect of gabazine was greater after exposures than before. This suggested that interneuronal GABA(A) receptors were desensitized, leading to an increased GABAergic input at dopaminergic cells. Thus, repetitive nitrogen exposure induced persistent changes in glutamatergic and GABAergic control of dopaminergic neurons, resulting in decreased activity of the nigrostriatal pathway.

Arterial baroreflex control during mild-to-moderate nitrous oxide narcosis.

We hypothesized that light-to-moderate inert gas narcosis might play a role in bradycardia in divers by altering sensitivity or response dynamics of arterial baroreflexes. Carotid-cardiac and carotid-mean arterial pressure (MAP) baroreflex response curves were generated by applying multiple levels of neck pressure and suction. Seven healthy volunteers were studied during air breathing (control) and during inhalation of 39% nitrous oxide (N2O). Baseline (pre-stimulus) heart rate (HR) and MAP were not altered by N2O. Range, threshold level, saturation level, and delay of responses did not differ between conditions. For hypertensive stimuli, sensitivity of responses did not differ between air control and N2O inhalation, but for hypotensive stimuli, maximal response gain for HR tended to be reduced with N2O inhalation (P = 0.054). Our results speak against inert gas narcosis as a primary mechanism for hyperbaric bradycardia, but it remains possible that an attenuation of tachycardic responses to hypotensive stimuli plays a role.

[Involvement of adrenergic mechanisms in developing the nervous syndrome of high pressure and nitrogen narcosis]. / Uchastie adrenergicheskikh mekhanismov v razvitii nervnogo sindroma vysokikh davlenii i azotnogo narkoza.

Involvement of the adrenergic mediator system in central mechanisms of hyperbaric nitrogen narcosis or the high pressure nervous syndrome (NSHP) produced by nitrogen or heliox gas mixtures under increased pressure was studied in mice and rabbit experiments with the use of pharmacological substances-analyzers. Accumulated data are indicative of lack of a significant role of the adrenergic system in the NSHP genesis and a protective effect of activation of the central but not peripheric adrenergic mediation in development of the behavioural and electrophysiological symptomatics of nitrogen narcosis. Mechanisms of NSHP and nitrogen narcosis and possible principles of pharmacological correction are under discussion.

Neuropsychologic and cardiovascular effects of clemastine fumarate under pressure.

Allergic rhinitis and mild respiratory infections have been widely accepted as temporary contraindications for fitness to dive. Nonetheless, several sport and professional divers use antihistamines to ease ear, nose, and throat (ENT) problems, especially for opening tubal ostium. Some divers know they are unfit to dive, but for a variety of reasons (e.g., money or short holiday) they try to clear their ears. Thus, the use of antihistaminic drugs (like clemastine fumarate) is common during diving. This double-blind, crossover study indicates that this special antihistamine does not increase the sedative effects of nitrogen narcosis, nor does it increase the level of cardiac arrhythmias. Liberal use of antihistamines while diving cannot be recommended because of possible complications connected with different preparations and the temporary limitations they impose on the diver.

Dissociation of the effects of alcohol and amphetamine on inert gas narcosis using reaction time and P300 latency.

Alcohol exacerbates and amphetamine ameliorates the slowing of reaction time (RT) produced by inert gas narcosis. The event-related brain potential P300 was used to determine whether these drug effects involve stimulus- or response-related processes, since P300 largely reflects the time to evaluate a stimulus while RT reflects this time plus the time to select and execute a response. Subjects breathed nitrous oxide (N2O) alone and in combination with ethyl alcohol or dextroamphetamine while responding to visually presented names that differed in probability (the oddball paradigm). N2O slowed P300, but this measure was comparatively insensitive to the exacerbation and amelioration that were indexed by RT. Relative to N2O alone, an RT-P300 difference was found for amphetamine + N2O but not for alcohol + N2O. We conclude that exacerbation involves both stimulus- and response-related processes but amelioration involves only the latter. This pattern of results can be explained by a model in which the drugs modulate slowing via the two energetical dimensions of arousal and activation, which influence stimulus- and response-related processes, respectively.

Opposing effects of anesthetics on pressure tolerance and compression rate effect.

Inert gas narcotics increase intrinsic pressure tolerance (1,000Pc) in CD-1 mice but interfere with development of the protective responses raising seizure thresholds during slower compression (e.g., 60Pc). This secondary narcotic effect can block up to 40% of the total attainable increase in Pc. The narcosis susceptible moiety of this compression rate effect develops early, whereas a narcosis resistant remnant accounts for increase in Pc occurring after 90 min of compression or pressure exposure. Pressure conditioning by multiday pressure exposure entails increases in both 60Pc and 1,000Pc and in virtual annullment of the compression rate effect. The effect can be completely blocked by narcotic gases in the conditioning atmosphere. In addition to blocking part of the compression rate effect the presence of narcotic gases under these conditions can reverse the effects of previously established pressure conditioning. 60Pc regresses much more slowly under these conditions than 1,000Pc. Either reversal rate is much more rapid in air at 1 ATA than at 80 ATA under 0.9 atm N2O. The implications of these data are discussed with regard to evaluation of the hypothesis of antagonism between inert gas narcotics and high pressures and to elaboration of the monoamine hypothesis to account for the modification of the compression rate effect by narcotic gases.

Observations after loss of consciousness under water.

Two diving incidents were investigated in which 1) an experienced professional diver (A) lost consciousness during an air dive to 69 meters, and 2) an amateur sports diver (D) lost consciousness during a 40-meter air dive. In subsequent tests both divers' ventilatory responses to inspired carbon dioxide were found to be extremely low. Under simulated diving conditions, Divers A and D exhibited marked carbon dioxide retention during exercise at 30 meters (end-tidal PCO2 = 65 and 57 mmHg, respectively) and at 70 meters, Diver A stopped work in less than 3 min because of severe dizziness. Reduced sensitivity to carbon dioxide, perhaps caused by the interaction of hypercapnia and nitrogen narcosis, is thought to have been partly responsible for these incidents.

Aseptic bone necrosis in Japanese divers.

Medical examination was performed on the divers in Ohura for 7 years from 1969 to 1972. Aseptic bone necrosis was found in 268 of 450 divers (59.5%). Men with over 5 years of experience in diving were highly affected (more than 54.4%). These bone lesions were found most frequently in the proximal end of the femur and the humerus. There was a significantly higher incidence of bone lesions in the men who dived over 30 meters. In the group of men with one or more bone lesions, 73.1% were known to have been treated for bends. The bone, once exposed to a certain compression of air, would have a tendency to develop bone lesions even after cessation of diving. Type A2 (linear opacity) led to the structural failure of the joint surface of the femur and the humerus. Histopathological study was carried out on the sections of bone obtained from three autopsy cases and four operated cases. Formation of air bubbles in the bone marrow cavity seemed to be the most important as the cause for the occurrence of aseptic bone necrosis, and local circulatory disturbance might be the most responsible for the progression of the bone lesion.

Helium pressure effects on avoidance behavior in rats breathing high nitrogen pressures.

3 rats given avoidance training and then exposed to 7, 13, and 19 ATA breathing nitrogen, then to 25, 31, and 37 ATA breathing helium, showed increased avoidance response rates above established baselines to 19 ATA followed by a decline. Narcotic effects of nitrogen were not reduced differentially by addition of helium.

Effect of nitrogen narcosis on cortical and subcortical evoked responses in the cat.

Four cats were chronically implanted with gross, monopolar electrodes in the lateral geniculate nucleus (LGN), pretectum-superior colliculus (P-SC), primary visual cortex (VI), and secondary visual cortex (VII). Following recovery and preliminary testing, the animals were dived in a dry hyperbaric chamber to the sea water equivalent of 103 m (i.e. 340 ft.) where visual evoked responses were recorded. No decrements in the amplitude of the visual evoked response were found at the LGN, but significant decreases did occur at the other three sites. These data suggested: 1) that the effects of nitrogen narcosis on the visual system are primarily central, and not simply peripheral in nature; 2) that these effects are not limited to the visual cortical mantle; and 3) that the narcosis apparently influences structures involving different anatomical levels of the brain which presumably mediate various types of visual processes. The findings were discussed as they relate to current ideas concerning the underlying neurological causes and behavioral effects of nitrogen narcosis.