Jean-Claude Rostain

Could hyperoxic ventilation impair oxygen delivery in septic patients

Objective:  In critically ill patients, a decrease in whole body oxygen consumption under hyperoxia has been reported and this could be related to hyperoxia‐induced arterial changes. We investigated changes in brachial artery circulation and tone during short‐term hyperoxic ventilation in septic patients.

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.

Nitrous oxide reverses the increase in striatal dopamine release produced by N-methyl-d-aspartate infusion in the substantia nigra pars compacta in rats

Bilateral administration of NMDA (5 x 10(-10) mol) in the substantia nigra pars compacta increases the striatal dopamine (DA) release. However, this enhancing effect of NMDA was suppressed by nitrous oxide exposure at 0.1 MPa, which induced per se a decrease of the DA release. These results show that nitrous oxide exerts a reversal effect on the increase in striatal DA release produced by NMDA receptor activation in the substantia nigra pars compacta. This observation may be related to the fact that nitrous oxide is thought to produce its effects by acting as an NMDA receptor antagonist.

High pressure enhanced NMDA activity in the striatum and the globus pallidus: relationships with myoclonia and locomotor and motor activity in rat.

In mammals high pressure of helium-oxygen (He-O2) breathing mixture leads to the high pressure neurological syndrome (HPNS) which includes a set of behavioural disorders such as locomotor and motor hyperactivity (LMA) and myoclonia. In rats, i.c.v. administrations of competitive NMDA antagonists decrease some of these symptoms suggesting that He-O2 pressure could enhance NMDA neurotransmission within the central nervous system. More recently, we have shown using microdialysis that the extracellular glutamate level is increased in the striatum by He-O2 pressure. Neurochemical data have suggested that this structure is probably involved in the LMA development but not in the myoclonia expression. When considering myoclonia, recent neuropathological studies performed at normal pressure in humans suggest that the globus pallidus extern (equivalent to the globus pallidus in the rat) could be involved in this behavioural disorder. The aim of this study was to compare the role of striatal and pallidal NMDA activity on the LMA development and the myoclonia expression in the model of rat exposed to 8 MPa of He-O2 mixture. The intrastriatal administration of D(-)-2-amino-7-phosphonoheptanoic acid (2-APH) (10 nmol/slide) reduced the LMA development but only slightly reduced myoclonia. In contrast, the intrapallidal administration of 2-APH (10 nmol/slide) reduced both LMA and myoclonia. These results suggest that the LMA development requires NMDA activity at both striatal and pallidal level. In contrast, the myoclonia expression mainly requires NMDA activity at pallidal level. Consequently, NMDA neurotransmission at input and output levels of the striato-pallidal pathway play different roles in some of the behavioural disorders induced by He-O2 pressure.

Pressure induces striatal serotonin and dopamine increases: a simultaneous analysis in free-moving microdialysed rats

High pressure is known as a basic etiological factor underlying central nervous system changes known as the high pressure neurological syndrome (HPNS). In the rat, HPNS includes behavioural disturbances including locomotor and motor hyperactivities (LMA) linked to a striatal dopamine (DA) increase. Recent findings have shown that intracerebroventricular administration of 5-HT3 or 5-HT1b antagonists decrease both LMA and striatal DA increase suggesting that pressure could enhance the serotonin (5-HT) neurotransmission. In this study, for the first time, the striatal levels of DA and 5-HT were simultaneously monitored using microdialysis in free-moving rats exposed to high pressure. Our results show that the striatal 5-HT level increases during pressure exposure. These data suggest that pressure-induced striatal 5-HT increase could participate in the increasing DA release. Nevertheless, the lack of correlation between striatal DA and 5-HT changes suggests that other processes are involved in the pressure-induced striatal DA increase.

A New System Analysis of Motor and Locomotor Activities Associated With a Microdialysis Study of Pressure-Induced Dopamine Increase in Rats

In this work, we report a new analysis system to quantify the behavioral disorders observed in the model of the rat submitted to high pressure and monitored by piezoelectric sensor. The major advance consists in a spectral 3D representation of LMA and tremor, which provides a better selectivity than previous systems. This behavioral processing indicated that tremor is characterized by a 7-14 Hz frequency band and LMA by a 20-35 Hz frequency band. The association of this system to the microdialysis technique to simultaneously evaluate the striatal DA level confirms that pressure-induced striatal DA increase is in great part linked to the LMA, and supports the concept of a complex ethiology for this symptom. We conclude that this new behavioral system analysis associated with microdialysis study constitutes a powerful tool to investigate the role of different neurotransmitters in the occurrence of the behavioral components described in the HPNS of rats.

Effects of repeated hyperbaric nitrogen–oxygen exposures on the striatal dopamine release and on motor disturbances in rats

Previous studies have demonstrated disruptions of motor activities and a decrease of extracellular dopamine level in the striatum of rats exposed to high pressure of nitrogen. Men exposed to nitrogen pressure develop also motor and cognitive disturbances related to inert gas narcosis. After repetitive exposures, adaptation to narcosis was subjectively reported. To study the effects of repetitive exposures to hyperbaric nitrogen-oxygen, male Sprague-Dawley rats were implanted in the striatum with multifiber carbon dopamine-sensitive electrodes. After recovery from surgery, free-moving rats were exposed for 2 h up to 3 MPa of nitrogen-oxygen mixture before and after one daily exposure to 1 MPa of nitrogen-oxygen, for 5 consecutive days. Dopamine release was measured by differential pulse voltammetry and motor activities were quantified using piezo-electric captor. At the first exposure to 3 MPa, the striatal dopamine level decreased during the compression (-15%) to reach -20% during the stay at 3 MPa. Motor activities were increased during compression (+15%) and the first 60 min at constant pressure (+10%). In contrast, at the second exposure to 3 MPa, an increase of dopamine of +15% was obtained during the whole exposure. However, total motor activities remained unchanged as compared to the first exposure. Our results confirm that nitrogen exposure at 3 MPa led to a decreased striatal dopamine release and increased motor disturbances in naïve rats. Repetitive exposures to 1 MPa of nitrogen induced a reversal effect on the dopamine release which suggests a neurochemical change at the level of the neurotransmitter regulation processes of the basal ganglia. In contrast, motor activity remained quantitatively unchanged, thus suggesting that dopamine is not involved alone in modulating these motor disturbances.

Microdialysis study of striatal dopaminergic dysfunctions induced by 3 MPa of nitrogen- and helium-oxygen breathing mixtures in freely moving rats

Previous studies have demonstrated opposite effects of high-pressure helium and nitrogen on extracellular dopamine (DA) levels, which may reflect disturbances on the synthesis, release or metabolic mechanisms. Intrastriatal microdialysis was used to measure the precursor (tyrosine), DA and its metabolites (DOPAC, HVA) levels under nitrogen- or helium- at pressure up to 3 MPa. Under 3 MPa of helium-oxygen breathing mixtures, the extracellular concentration of tyrosine is decreased while the extracellular concentration of DA is increased. On the contrary, nitrogen-oxygen breathing mixture at the same pressure increased extracellular tyrosine concentration and decreased DA release. Under both conditions, an increment of the DOPAC and HVA levels could be noted. Our results suggest that changes in DA release and metabolism during high-pressure helium exposure reflect the effect of the pressure per se, whereas the intrinsic effects of narcotic gases, although sensitive to pressure, would be revealed by hyperbaric nitrogen exposure.

The full expression of locomotor and motor hyperactivities induced by pressure requires both striatal dopaminergic and N-methyl-D- asparate receptor activities in the rat

High pressure induced locomotor and motor hyperactivities (LMA), tremor and myoclonia in rat. The LMA has been reported to be reduced by intracerebroventricular (i.c.v.) administration of dopaminergic receptor antagonists. Moreover, the LMA but not myoclonia correlate with pressure induced striatal dopamine increase. Nevertheless the role of dopaminergic and NMDA receptor activities at striatal level in the development of LMA remained unclear. In this study, the microdialysis technique associated to a behavioural device was used to test the effects of intra-striatal administration of D1 antagonist SCH23390 (1 microM), D2 antagonist sulpiride (1 microM) and NMDA antagonist AP-5 (10 microM) on LMA, tremor and myoclonia expression. Data clearly showed that LMA was drastically reduced by each treatment. In contrast, tremor and myoclonia were poorly affected. These data suggest that both dopaminergic and NMDA receptor activities at striatal level are needed for the full expression of the pressure-induced LMA and confirm that striatal neurotransmission changes are principally involved in this behavioural disorders. At the light of recent studies on dopaminergic neurotransmission and glutamate evoked-NMDA activity, we suggest that blockage of D1 or D2 receptors should reduced the LMA by reducing glutamate-evoked activity.

Role of 5-HT1b receptor in the pressure-induced behavioral and neurochemical disorders in rats.

When human divers and experimental animals are exposed to increasing environmental pressure, they develop the high-pressure neurologic syndrome (HPNS) that has been recently demonstrated to include an increase in striatal dopamine (DA) release. This increase has been correlated with enhanced locomotor and motor activity (LMA). In the present study, we investigated the effect of the 5-HT1b receptor antagonist (+/-)cyanopindolol, which has been shown to block at normal pressure the increase in striatal DA release induced by the administration of the 5-HT1b receptor agonist CGS 12066B. Our data clearly showed that the administration of (+/-)cyanopindolol partially blocked both the pressure-induced increase in striatal DA release and the development of LMA. These results suggest the contribution of the 5-HT neurotransmission in the DA-related neurochemical and behavioral disorders that occur in rats exposed to high pressure.