Clinical and echocardiographic predictors of embolism in infective endocarditis: systematic review and meta-analysis.

OBJECTIVES: Prediction of embolic events (EEs) in infective endocarditis (IE) could inform clinical decisions, such as surgical timing. We conducted a systematic review to more precisely define associations between risk factors and EEs. METHODS: We searched two bibliographic databases (1994-2018) for observational studies that reported EEs in IE patients and considered clinical, microbiological or echocardiographic risk factors. Studies that did not use Duke criteria or only investigated a subset of IE patients were excluded. Study quality was assessed using the Newcastle-Ottawa scale. A pooled risk ratio (RR) for each risk factor was estimated using random-effects models; statistical heterogeneity was estimated using I2. RESULTS: Of 3862 unique citations, 47 cohort studies (11 215 IE cases) were included; 54 risk factors were analysed in at least two studies, with nine studies reporting other individual factors. Most studies were of high methodological quality. Major predictors of EEs were intravenous drug use (RR 1.69, 95% CI 1.32-2.17; I2 = 46%), Staphylococcus aureus infection (RR 1.64, 95% CI 1.45-1.86, I2 = 32%), mitral valve vegetation (RR 1.24, 95% CI 1.11-1.37, I2 = 30%), and vegetation size >10 mm (RR 1.87, 95% CI 1.57-2.21, I2 = 48%). EE risk was also higher with human immunodeficiency virus, chronic liver disease, elevated C-reactive protein, Staphylococcus spp. infection, vegetation presence, and multiple, mobile or prosthetic mechanical valve vegetation, and lower with Streptococcus spp. infection. Most findings were unchanged in sensitivity analyses that removed studies with pulmonary EEs from the outcome. CONCLUSIONS: Given the serious consequences of embolism, surgical evaluation may be considered in patients with these risk factors.

Examination of the Role of NMDA and GABAA Receptors in the Effects of Hyperbaric Oxygen on Striatal Dopamine Levels in Rats.

Hyperbaric oxygen induced in rats a decrease in striatal dopamine levels. Such decrease could be a result of changes in glutamatergic and GABAergic controls of the dopaminergic neurons into the Substantia Nigra Pars Compacta. The aim of this study was to determine the role of gluatamatergic and Gama-Amino-Butyric-Acid neurotransmissions in this alteration. Dopamine-sensitive electrodes were implanted into the striatum under general anesthesia. After one week rest, awaked rats were exposed to oxygen-nitrogen mixture at a partial pressure of oxygen of 3 absolute atmospheres. Dopamine level was monitored continuously (every 3 min) by in vivo voltammetry with multifiber carbon electrodes before and during hyperbaric oxygen exposure. Hyperbaric oxygen induced a decrease in dopamine level in relationship with the increase in partial pressure of oxygen (-40% at 3 ATA). The used of N-Methyl-D-Aspartate, agonist of glutamatergic N-Methyl-D-Aspartate receptors did not improve considerably this change and gabazine antagonist of Gama-Amino-Butyric-Acid-a receptors induced some little alteration of this change. These results suggest the involvement of other mechanisms.

A review of recent neurochemical data on inert gas narcosis.

Nitrogen narcosis occurs in humans at around 0.4 MPa (4 ATA). Hydrogen narcosis occurs between 2.6 and 3.0 MPa. In rats, nitrogen disturbances occur from 1 MPa and a loss of righting reflex around 4 MPa. Neurochemical studies in striatum of rats with nitrogen at 3 MPa (75% of anesthesia threshold) with differential pulse voltammetry have demonstrated a decrease in dopamine (DA) release by neurons originated from the substantia nigra pars compacta (SNc). Such a decrease is found also with compressed argon, which is more narcotic than nitrogen and with the anesthetic gas nitrous oxide. Inversely, compressed helium with its very low narcotic potency induces DA increase. Microdialysis studies in the striatum have indicated that nitrogen also induces a decrease of glutamate concentration. Nitrogen pressure did not modify NMDA glutamate receptor activities in SNc or striatum but enhanced GABAA receptors activities in SNc. Repetitive exposures to nitrogen narcosis suppressed the DA decrease and induced an increase. This fact and the lack of improvement of motor disturbances did not support the hypothesis of a physiological adaptation. The desensitization of the GABAA receptors on DA cells during recurrent exposures and the parallel long-lasting decrease of glutamate coupled to the increase in NMDA receptor sensitivity suggest a nitrogen neurotoxicity or addiction induced by recurrent exposures. The differential changes produced by inert gases indifferent neurotransmitter receptors would support the binding protein theory.

Post effect of repetitive exposures to pressure nitrogen-induced narcosis on the dopaminergic activity at atmospheric pressure.

Nitrogen at pressure produces a neurological syndrome called nitrogen narcosis. Neurochemical experiments indicated that a single exposure to 3 MPa of nitrogen reduced the concentration of dopamine by 20% in the striatum, a structure involved in the control of extrapyramidal motor activity. This effect of nitrogen was explained by enhanced GABAergic neurotransmission through GABAA receptors and, to a lesser extent, by a decreased glutamatergic input to DA cells through NMDA receptors. The aim of this study was to study, under normobaric conditions, possible alterations of NMDA receptor activity in the substantia nigra pars compacta (SNc) induced by repetitive exposures to nitrogen pressure. Under general anesthesia, male Sprague-Dawley rats were implanted in the striatum with multifiber carbon dopamine-sensitive electrodes and in the SNc with guide cannulae for drug injections. After recovery from surgery, the striatal dopamine level was recorded by voltammetry in freely-moving rats, in normobaric conditions, before and after 5 repetitive exposures to 1MPa of nitrogen (threshold of nitrogen narcosis occurrence in rat). The effect of NMDA receptor activity on DA concentration was investigated using agonist (NMDA) and specific antagonist (AP7) SNc administration. Following repetitive nitrogen exposures, the ability of NMDA to elevate DA concentrations was enhanced. In contrast, after nitrogen exposure AP7 produced a paradoxical increase in DA concentration compared to its inhibitory effect before any exposure. Similar responses were obtained after a single exposure to 3MPa nitrogen. Thus, repetitive exposures to nitrogen narcosis produced a sensitization of postsynaptic NMDA receptors on DA cells, related to a decreased glutamatergic input in SNc. Consequently, successive nitrogen narcosis exposures disrupted ion-channel receptor activity revealing a persistent nitrogen-induced neurochemical change underlying the pathologic process.

Effects of NMDA administration in the substantia nigra pars compacta on the striatal dopamine release before and after repetitive exposures to nitrogen narcosis in rats.

Hyperbaric nitrogen-oxygen exposure developed in rats a decrement of the striatal dopamine release, which was reversed by repetitive exposures. This dopamine decrease could be the result of the antagonistic effect of nitrogen on NMDA receptors. The increment of the dopamine release, following repetitive exposures to nitrogen, could be attributed to a desensitisation of NMDA receptors to the effects of nitrogen. To test these hypotheses, male Sprague-Dawley rats were implanted with electrodes in the striatum to measure dopamine release by voltammetry and cannula in the substantia nigra pars compacta for NMDA injection. Free-moving rats were exposed up to 3MPa of nitrogen-oxygen mixture before and after 5 exposures to 1MPa. At the first exposure to 3MPa, the dopamine level decreased (-15%) but is counteracted by NMDA administration. In contrast, after repetitive exposure, the second exposure to 3MPa, induces a 10% dopamine increase. NMDA administration significantly potentiated this increase. Our results neither support the hypothesis of an antagonist effect of nitrogen on NMDA receptors at the first exposure, nor that of a NMDA receptor desensitization following repetitive exposures to hyperbaric nitrogen.