Hyperoxia Improves Hemodynamic Status During Head-up Tilt Testing in Healthy Volunteers A Randomized Study

International audienceHead-up tilt test is useful for exploring neurally mediated syncope. Adenosine is an ATP derivative implicated in cardiovascular disturbances that occur during head-up tilt test. The aim of the present study was to investigate the impact of hyperoxia on adenosine plasma level and on hemodynamic changes induced by head-up tilt testing. Seventeen healthy male volunteers (mean age 35 AE 11 years) were included in the study. The experiment consisted of 2 head-up tilt tests, 1 session with subjects breathing, through a mask, medical air (FiO 2 ¼ 21%) and 1 session with administration of pure oxygen (FiO 2 ¼ 100%) in double-blind manner. Investigations included continuous monitoring of hemodynamic data and measurement of plasma adenosine levels. No presyncope or syncope was found in 15 of the 17 volunteers. In these subjects, a slight decrease in systolic blood pressure was recorded during orthostatic stress performed under medical air exposure. In contrast, hyperoxia led to increased systolic blood pressure during orthostatic stress when compared with medical air. Furthermore, mean adenosine plasma levels decreased during hyperoxic exposure before (0.31 AE 0.08 mM) and during head-up tilt test (0.33 AE 0.09 mM) when compared with baseline (0.6 AE 0.1 mM). Adenosine plasma level was unchanged during medical air exposure at rest (0.6 AE 0.1 mM), and slightly decreased during orthostatic stress. In 2 volunteers, the head-up tilt test induced a loss of consciousness when breathing air. In these subjects, adenosine plasma level increased during orthostatic stress. In contrast, during hyperoxic exposure, the head-up tilt test did not induce presyncope or syncope. In these 2 volunteers, biological study demonstrated a decrease in adenosine plasma level at both baseline and during orthostatic stress for hyperoxic exposure compared with medical air. These results suggest that hyperoxia was able to increase blood pressure during head-up tilt test via a decrease in plasma adenosine concentration. Our results also suggest that adenosine receptor antagonists are worth trying in neurocardiogenic syncope. (Medicine 95(8):e2876) Abbreviations: AR = adenosine receptor, APL = adenosine plasma level, BP = blood pressure, DBP = diastolic blood pressure, FiO 2 = fraction of inspired oxygen, HR = heart rate, HUT = head-up tilt test, LMM = linear mixed model, PO 2 = partial pressure of oxygen, SBP = systolic blood pressure

Nitrogen at raised pressure interacts with the GABAA receptor to produce its narcotic pharmacological effect in the rat

Background: Strong evidence supports the concept that conventional anesthetics, including inhalational agents and inert gases, such as xenon and nitrous oxide, interact directly with ion channel neurotransmitter receptors. However, there is no evidence that nitrogen, which only exhibits narcotic potency at increased pressure, may act by a similar mechanism. Methods: We compared the inhibitory and sedative effects of ␥-aminobutyric acid (GABA) and nitrogen pressure on locomotor activity and striatal dopamine release in freely moving rats and investigated the pharmacologic properties of the GABAinduced and nitrogen pressure-induced narcotic action using the highly selective competitive GABA A receptor antagonist bicuculline. Results: Intracerebroventricular GABA infusion up to 60 mol or exposure to nitrogen pressure up to 3 MPa decreased to a similar extent striatal dopamine release (

Implication de la neurotransmission glutamatergique dans la sensibilisation comportementale à court terme aux amphétamines

Bien que la neurotransmission glutamatergique joue un rôle pivot dans le développement et l expression de la sensibilisation comportementale aux amphétamines, le rôle spécifique de certaines structures glutamatergiques qui projettent sur l aire tegmentale ventrale et/ou le noyau accumbens n est pas encore bien caractérisé. Nous montrons que l hippocampe dorsal, la partie prélimbique du cortex préfrontal et l amygdale basolatérale joue un rôle prépondérant dans les réponses locomotrices induites par l administration aiguë (développement de la sensibilisation) et chronique (expression de la sensibilisation) d amphétamines, suggérant les réponses locomotrices aux amphétamines impliquent un ensemble de structures glutamatergiques corticolimbiques. Par la suite, nous nous sommes intéressés au rôle de la neurotransmission glutamatergique associée aux récepteurs NMDA dans le noyau accumbens, qui est considéré comme le noyau clé de l expression de la sensibilisation, sur le développement à court terme de la sensibilisation aux amphétamines. De plus, nous montrons le développement de la sensibilisation à court terme aux amphétamines requiert l activation concomitante de certains récepteurs NMDA au glutamate et nicotiniques à l acétylcholine dans le noyau accumbens. De plus, l activation concomitante de ces récepteurs sous tend également la libération de dopamine induite par les amphétamines dans le noyau accumbens. L ensemble de ces données montre que la neurotransmission glutamatergique, et les structures glutamatergiques qui projettent sur l aire tegmentale ventrale et/ou le noyau accumbens, joue un rôle majeur dans la sensibilisation comportementale à court terme aux amphétamines.Although it is well admitted that the glutamatergic neurotransmission plays a pivotal role in the development and expression of behavioral sensitization to amphetamine, the specific role of glutamatergic structures that project to the ventral tegmental and/or the nucleus accumbens is less well studied. We showed that the dorsal hippocampus, the prelimbic part of the prefrontal cortex and the basolateral amygdala play a critical role in both acute (development of sensitization) and chronic (expression of sensitization) locomotor responses induced by amphetamine, suggesting that behavioral responses to amphetamine are mediated by circuitry of corticolimbic glutamatergic structures. Next, we investigated the role of glutamatergic NMDA receptors contained in the nucleus accumbens, which is seen as the key structure for the expression of sensitization, in the development of short term sensitization to amphetamine. Interestingly, we showed that, contrasting with the current dichotomous thinking that has attributed specialized functions to the ventral tegmental area and the nucleus accumbens, respectively in the development and the expression of behavioral sensitization, concomitant activation of certain types of NMDA and nicotinic receptors in the nucleus accumbens is also required for the development of short term sensitization. Furthermore, we showed that concomitant activation of these receptors sustained the amphetamine-induced dopamine release in the nucleus accumbens. All these data show that glutamatergic neurotransmission, and glutamatergic structures which project onto mésoaccumbens system, plays a major role in short-term behavioral sensitization to amphetamine.AIX-MARSEILLE2-Bib.electronique (130559901) / SudocSudocFranceF

La plongée : pression barométrique et mécanismes neurochimiques

Les travaux de Paul Bert regroupés dans son ouvrage "La Pression Barométrique" en 1878 ont été à l'origine de la physiologie hyperbare moderne en démontrant 1) que l'on devait dissocier les effets de la pression de ceux de la décompression, 2) les effets de l'oxygène sous pression et 3) que les accidents neurologiques et mortels des plongeurs étaient dus à des décompressions trop rapides. Cependant, il fallut attendre les travaux de Behnke et al. en 1935, pour que l'on attribue les troubles observés en air comprimé ou en mélange azote-oxygène à partir de 3 bars de pression, à l'augmentation de pression partielle d'azote entraînant une narcose à l'azote. On connaît peu de chose sur les origines et les mécanismes de la narcose que l'on retrouve avec tous les gaz dits inertes. La conception traditionnelle était de relier, comme en anesthésie, l'apparition de la narcose à l'expansion des sites hydrophobiques membranaires au delà d'un volume critique du fait de l'adsorption des molécules du gaz. L'observation d'un effet inverse de la pression sur l'anesthésie générale a longtemps conforté cette théorie lipidique. Cependant, depuis peu, on considère à nouveau les hypothèses protéiques depuis que des résultats avec des anesthésiques gazeux ont été interprétés comme l'évidence d'une interaction directe gaz - protéine. La question est de savoir si les gaz inertes qui perturbent notamment la neurotransmission dopaminergique et GABAergique et probablement glutamatergique, agissent par des processus de liaison sur les protéines des récepteurs aux neurotransmetteurs

Narcose à l'azote (modulation de la neurotransmission striatale chez le rat et implication des canaux potassiques TREK-1 chez la souris)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Implication des récepteurs NMDA et GABAa dans le contrôle du système dopaminergique nigro-strié chez le rat soumis à la narcose à l'azote, avant et après des expositions répétées

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

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

International audienceNitrogen-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

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

International audienceNitrogen-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