Tirofiban, a Glycoprotein IIb/IIIa Antagonist, Has a Protective Effect on Decompression Sickness in Rats: Is the Crosstalk Between Platelet and Leukocytes Essential?

In its severest forms, decompression sickness (DCS) may extend systemically and/or induce severe neurological deficits, including paralysis or even death. It seems that the sterile and ischemic inflammatory phenomena are consecutive to the reaction of the bubbles with the organism and that the blood platelet activation plays a determinant role in the development of DCS. According to the hypotheses commonly put forward, the bubbles could either activate the platelets by direct contact or be the cause of abrasion of the vascular epithelium, which would expose the basal plate glycogen and then prompt the platelets to activate. The purpose of this study is to confirm anti-platelet drugs specific to GPIIb/IIIa integrin could prevent DCS, using a rat model. There is a significant difference concerning the incidence of the drug on the clinical status of the rats (p = 0.016), with a better clinical outcome for rats treated with tirofiban (TIR) compared with the control rats (p = 0.027), even if the three anti-GPIIb/IIIa agents used have limited respiratory distress. TIR limited the decrease in platelet counts following the hyperbaric exposure. TIR help to prevent from DCS. TIR is specific to GPIIb/IIIa whereas eptifibatide and abciximab could inhibit αVβ3 and αMβ2 involved in communication with the immune system. While inhibiting GPIIb/IIIa could highlight a platelet-dependent inflammatory pathway that improves DCS outcomes, we wonder whether inhibiting the αVβ3 and αMβ2 communications is not a wrong approach for limiting mortality in DCS

Implication d'un shunt circulatoire droite-gauche dans les lésions cérébrales latentes chez les plongeurs

Nous avons cherché à décrire le rôle joué par un shunt circulatoire droite-gauche dans la survenue de lésions cérébrales latentes chez les plongeurs. Dix plongeurs, professionnels et sportifs, indemnes d'accident de désaturation avec un minimum de 500 plongées nous ont été adressés par des médecins des sports que nous avions contactés par courrier. Douze jeunes militaires non plongeurs constituaient le groupe témoin. Nous avons recherché la présence d'un shunt droite-gauche par écho Doppler transcrânien. Les lésions cérébrales correspondaient à des hypersignaux de la substance blanche retrouvés à la fois sur les séquences T2 et FLAIR en IRM. On ne réussit pas à mettre en évidence un lien entre la présence d'un tel shunt droite-gauche et la présence d'hypersignaux chez les plongeurs indemnes d'accident de désaturation neurologique aigu. Cependant on a tendance à retrouver une plus grande prévalence de ces hypersignaux en présence d'un shunt de haut grade. En outre alors que la différence n'est pas significative entre le groupe plongeur et le groupe témoin, on trouve significativement plus d'hypersignaux chez les plongeurs les plus expérimentés indépendamment de la présence ou de l'absence de shunt. On propose la réalisation d'une étude sur des plongeurs beaucoup plus expérimentés que ceux des études conduites jusqu'à présent et porteurs de shunts de haut grade

Implication d'un shunt circulatoire droite-gauche dans les lésions cérébrales latentes chez les plongeurs

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocPARIS-Bib. Serv.Santé Armées (751055204) / SudocSudocFranceF

Gut fermentation seems to promote decompression sickness in humans

International audienceMassive bubble formation after diving can lead to decompression sickness (DCS) that can result in neurological disorders. In experimental dives using hydrogen as the diluent gas, decreasing the body's H2 burden by inoculating hydrogen-metabolizing microbes into the gut reduces the risk of DCS. In contrast, we have shown that gut bacterial fermentation in rats on a standard diet promotes DCS through endogenous hydrogen production. Therefore, we set out to test these experimental results in humans. Thirty-nine divers admitted into our hyperbaric center with neurological DCS (Affected Divers) were compared with 39 healthy divers (Unaffected Divers). Their last meal time and composition were recorded. Gut fermentation rate was estimated by measuring breath hydrogen 1-4 h after the dive. Breath hydrogen concentrations were significantly higher in Affected Divers (15 ppm [6-23] vs. 7 ppm [3-12]; P = 0.0078). With the use of a threshold value of 16.5 ppm, specificity was 87% [95% confidence interval (CI) 73-95] for association with neurological DCS onset. We observed a strong association between hydrogen values above this threshold and an accident occurrence (odds ratio = 5.3, 95% CI 1.8-15.7, P = 0.0025). However, high fermentation potential foodstuffs consumption was not different between Affected and Unaffected Divers. Gut fermentation rate at dive time seemed to be higher in Affected Divers. Hydrogen generated by fermentation diffuses throughout the body and could increase DCS risk. Prevention could be helped by excluding divers who are showing a high fermentation rate, by eliminating gas produced in gut, or even by modifying intestinal microbiota to reduce fermentation rate during a dive

Colonic fermentation promotes decompression sickness in Rats.

International audienceMassive bubble formation after diving can lead to decompression sickness (DCS). During dives with hydrogen as a diluent for oxygen, decreasing the body’s H2 burden by inoculating hydrogen-metabolizing microbes into the gut reduces the risk of DCS. So we set out to investigate if colonic fermentation leading to endogenous hydrogen production promotes DCS in fasting rats. Four hours before an experimental dive, 93 fasting rats were force-fed, half of them with mannitol and the other half with water. Exhaled hydrogen was measured before and after force-feeding. Following the hyperbaric exposure, we looked for signs of DCS. A higher incidence of DCS was found in rats force-fed with mannitol than in those force-fed with water (80%, [95%CI 56, 94] versus 40%, [95%CI 19, 64], p < 0.01). In rats force-fed with mannitol, metronidazole pretreatment reduced the incidence of DCS (33%, [95%CI 15, 57], p = 0.005) at the same time as it inhibited colonic fermentation (14 ± 35 ppm versus 118 ± 90 ppm, p = 0.0001). Pre-diveingestion of mannitol increased the incidence of DCS in fasting rats when colonic fermentation peaked during the decompression phase. More generally, colonic fermentation in rats on a normal diet could promote DCS through endogenous hydrogen production

Case series of unusual neurologic symptoms after scubadiving training sessions, in the context of SARS COV2preventive measures and restrictions

International audienceIn July 2020, 8 young divers presented neurological symptoms during the first level of military diving training (« ship diver »course) at the French military diving school . Onset of symptoms ranged from 5 to 50 hours after a yo yo diving only one yo yo)of 10 min (total duration) at a depth of 30 meters ascent rate of 15m/min, no deco stops). The origin of these symptoms raises thequestion of whether they can be related to decompression sickness . Indeed, while yo yo diving is identified as a risk factor for theoccurrence of DCIS, it is in fact very rare in the context of training diving with these diving parameters. In addition, the late onsetof symptoms after diving is highly unusual in the case of DCS. In order to understand the reasons for this cluster of neurologicalsymptoms, a full investigation was carried out by the epidemiology department , not limited to the DCS hypothesis.Objectives: Description of the cases & results of the epidemiological investigation. DISCUSSION/CONCLUSIONAfter eliminating other diagnoses and taking into account the clinical evolution under HBOT, we retain the hypothesis of DCS with a multifactorialorigin Corrective measures have been implemented including a return to the dive planning of previous courses, maintaining moderate aerobic activity prior to diving, strict hydration guidelines and limiting force work onehour after diving Since then, no cluster of neurological symptoms has recurred The incidence of DCS has normalized to the usual low values The possible impact of CO 2 retention due to the use of the COVID mask is not yetdetermined CO 2 could promote the formation of gas nuclei and be involved in the delayed latency of symptoms A programme of experimental animal and human studies is underwa

Cecal Metabolomic Fingerprint of Unscathed Rats: Does It Reflect the Good Response to a Provocative Decompression?

International audienceOn one side, decompression sickness (DCS) with neurological disorders lead to a reshuffle of the cecal metabolome of rats. On the other side, there is also a specific and different metabolomic signature in the cecum of a strain of DCS-resistant rats, that are not exposed to hyperbaric protocol. We decide to study a conventional strain of rats that resist to an accident-provoking hyperbaric exposure, and we hypothesize that the metabolomic signature put forward may correspond to a physiological response adapted to the stress induced by diving. The aim is to verify and characterize whether the cecal compounds of rats resistant to the provocative dive have a cecal metabolomic signature different from those who do not dive. 35 asymptomatic diver rats are selected to be compared to 21 rats non-exposed to the hyperbaric protocol. Because our aim is essentially to study the differences in the cecal metabolome associated with the hyperbaric exposure, about half of the rats are fed soy and the other half of maize in order to better rule out the effect of the diet itself. Lower levels of IL-1β and glutathione peroxidase (GPX) activity are registered in blood of diving rats. No blood cell mobilization is noted. Conventional and ChemRICH approaches help the metabolomic interpretation of the 185 chemical compounds analyzed in the cecal content. Statistical analysis show a panel of 102 compounds diet related. 19 are in common with the hyperbaric protocol effect. Expression of 25 compounds has changed in the cecal metabolome of rats resistant to the provocative dive suggesting an alteration of biliary acids metabolism, most likely through actions on gut microbiota. There seem to be also weak changes in allocations dedicated to various energy pathways, including hormonal reshuffle. Some of the metabolites may also have a role in regulating inflammation, while some may be consumed for the benefit of oxidative stress management

Cecal Metabolomic Fingerprint of Unscathed Rats: Does It Reflect the Good Response to a Provocative Decompression?

International audienceOn one side, decompression sickness (DCS) with neurological disorders lead to a reshuffle of the cecal metabolome of rats. On the other side, there is also a specific and different metabolomic signature in the cecum of a strain of DCS-resistant rats, that are not exposed to hyperbaric protocol. We decide to study a conventional strain of rats that resist to an accident-provoking hyperbaric exposure, and we hypothesize that the metabolomic signature put forward may correspond to a physiological response adapted to the stress induced by diving. The aim is to verify and characterize whether the cecal compounds of rats resistant to the provocative dive have a cecal metabolomic signature different from those who do not dive. 35 asymptomatic diver rats are selected to be compared to 21 rats non-exposed to the hyperbaric protocol. Because our aim is essentially to study the differences in the cecal metabolome associated with the hyperbaric exposure, about half of the rats are fed soy and the other half of maize in order to better rule out the effect of the diet itself. Lower levels of IL-1β and glutathione peroxidase (GPX) activity are registered in blood of diving rats. No blood cell mobilization is noted. Conventional and ChemRICH approaches help the metabolomic interpretation of the 185 chemical compounds analyzed in the cecal content. Statistical analysis show a panel of 102 compounds diet related. 19 are in common with the hyperbaric protocol effect. Expression of 25 compounds has changed in the cecal metabolome of rats resistant to the provocative dive suggesting an alteration of biliary acids metabolism, most likely through actions on gut microbiota. There seem to be also weak changes in allocations dedicated to various energy pathways, including hormonal reshuffle. Some of the metabolites may also have a role in regulating inflammation, while some may be consumed for the benefit of oxidative stress management