Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness

Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder. Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013–June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia. We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P < 0.05) (mean ± standard-deviation: IPE: 53 ± 61 pmol/L; DCS: 15 ± 17; controls: 6 ± 3; IPE versus DCS or controls: P < 0.05); (ii) ischemia-modified albumin: 68% of IPE patients had a high level versus 16% of DCS patients (P < 0.05) (IPE: 123 ± 25 arbitrary-units; DCS: 84 ± 25; controls: 94 ± 7; IPE versus DCS or controls: P < 0.05); (iii) BNP: 53% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 383 ± 394 ng/L; DCS: 37 ± 28; controls: 19 ± 15; IPE versus DCS or controls: P < 0.01); (iv) cTnI: 63% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 0.66 ± 1.50 μg/L; DCS: 0.0061 ± 0.0040; controls: 0.0090 ± 0.01; IPE versus DCS or controls: P < 0.01). The combined “BNP-cTnI” levels provided most discrimination: all IPE patients, but none of the DCS patients, had elevated levels of either/both of these markers. We propose that antidiuretic hormone acts together with a myocardial ischemic process to promote IPE. Thus, monitoring of antidiuretic hormone and cardiac biomarkers can help to make a quick and reliable diagnosis of IPE

Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals

Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum (R2 = 0.041, Pcorr < 0.001) and cingulum (right: R2 = 0.041, left: R2 = 0.040, Pcorr < 0.001). Lithium medication, later onset and short disease duration were related to higher FA along multiple ROIs. Results of the meta-analysis showed similar effects. We demonstrated widespread WM abnormalities in BD and highlighted that altered WM connectivity within the corpus callosum and the cingulum are strongly associated with BD. These brain abnormalities could represent a biomarker for use in the diagnosis of BD. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org

Pharmacological profile of adenosine A2A receptors in cardiovascular diseases

L’athérosclérose est responsable de la diminution du diamètre des vaisseaux par formation d’une « plaque » constituée notamment de lipides limitant la circulation sanguine (ischémie) et l’oxygénation des tissus. L’adénosine est capable de réguler la fonction cardiovasculaire notamment par le biais de son récepteur A2A qui induit une vasodilatation permettant d’augmenter les apports sanguins. Une faible présence des A2AR semble marquer l’ischémie (sans spécificité de territoire) tandis que la présence de récepteurs de réserve (réponse biologique maximale malgré un faible nombre de sites occupés) signe une perturbation sévère au niveau du flux sanguin coronarien (ischémie inductible). Ces analyses pourront être faites sur un prélèvement sanguin classique. L’adénosine sanguine pourrait prédire le risque de décès lié à un choc cardiogénique compliquant la maladie initiale, où l’on retrouve une hypoperfusion des organes périphériques (dysfonction de la pompe cardiaque) que l’organisme tente de compenser par vasoconstriction (moins d’A2AR). Ces travaux laissent entrevoir la possibilité d’user du système adénosinergique tant au niveau diagnostic (absence de marqueur biologique d’ischémie et de coronaropathie fiable à ce jour), pronostic, qu’au niveau thérapeutique.Atherosclerosis is responsible for the decrease in the diameter of the vessels by formation of a "plaque" consisting in particular of lipids limiting the blood circulation (ischemia) and tissue oxygenation. Adenosine is able to regulate cardiovascular function, particularly through its A2A receptor, which induces vasodilation to increase blood intake. A low presence of A2AR seems to mark ischemia (without specificity of territory) while the presence of reserve receptors (maximum biological response despite a small number of occupied sites) sign a severe disturbance in the blood flow coronary (inducible ischemia). These analyzes can be done on a classic blood sample. Blood adenosine could predict the risk of death from cardiogenic shock complicating the initial disease, where peripheral organs are hypoperfused (cardiac pump dysfunction) that the body attempts to compensate for by vasoconstriction (less A2AR). This work suggests the possibility of using the adenosinergic system both at the level of diagnosis (absence of biological marker of ischemia and coronary artery disease reliable to date), prognosis, than at the therapeutic level

Expression des récepteurs à l’adénosine A2A dans les artères coronaires et les cellules mononucléées du sang périphérique de patients atteints de maladie coronarienne

Le système adénosinergique peut réguler le flux sanguin coronaire perturbé chez les patients atteints de maladie coronarienne essentiellement par le biais du récepteur à l’adénosine A2A. Nous avons étudié l’expression de ces récepteurs chez 20 patients devant subir un pontage au niveau des cellules mononucléées du sang périphérique (PBMCs) et des tissus aortiques et coronaires. L’expression des A2AR des PBMCs déterminée par Western Blot est plus faible chez les patients (0,83 +/-0,31 vs 1,2+/-0,35 UA ; p<0.01) et est corrélée avec celle des coronaires (r :0,77 avec p<0.,01) et de l’aorte (r : 0,59). Les taux de production d’AMPc (fonctionnalité des récepteurs) des PBMCs sont plus faibles chez les patients par rapport aux contrôles à l’état basal et en cas de stimulation par un agoniste sélectif (AMPc basal : 120+/-42 vs 191+/-65 et production maximale : 360+/-113 vs 560+/-215 pg/10⁶ cellules, p<0.05). Des résultats similaires sont obtenus sur l’aorte avec une augmentation de la production d’AMPc induite par l’agoniste de 246% (vs 300% dans les PBMCs).L’expression des A2AR sur les PBMCs est corrélée à celles de l’artère coronaire et de l’aorte. Elle est moins forte chez le sujet coronarien. L’activité des A2AR est également plus faible, mais la capacité de production maximale d’AMPc par rapport à la production basale n’est pas significativement différente. Les PBMCs sont donc le reflet de l’expression des A2AR au niveau coronaire, ce qui en ferait un biomarqueur diagnostique intéressant car non invasif dans le cadre de la maladie coronarienne. D’autres études sont nécessaires pour définir si leur utilité peut s’étendre à d’autres pathologies cardiovasculaires

Sudden Onset Nephrotic-Range Proteinuria

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Blood Adenosine Increase During Apnea in Spearfishermen Reinforces the Efficiency of the Cardiovascular Component of the Diving Reflex

International audienceThe physiopathology consequences of hypoxia during breath-hold diving are a matter of debate. Adenosine (AD), an ATP derivative, is suspected to be implicated in the adaptive cardiovascular response to apnea, because of its vasodilating and bradycardic properties, two clinical manifestations observed during voluntary apnea. The aim of this study was to evaluate the adenosine response to apnea-induced hypoxia in trained spearfishermen (SFM) who are used to perform repetitive dives for 4–5 h. Twelve SFM (11 men and 1 woman, mean age 41 ± 3 years, apnea experience: 18 ± 9 years) and 10 control (CTL) subjects (age 44 ± 7 years) were enrolled in the study. Subjects were asked to main a dry static apnea and stopped it when they began the struggle phase (average duration: SFM 120 ± 78 s, CTL 78 ± 12 s). Capillary blood samples were collected at baseline and immediately after the apnea and analyzed for standard parameters and adenosine blood concentration ([AD]b). Heart rate (HR), systolic (SBP), and diastolic (DBP) blood pressures were also recorded continuously during the apnea. During the apnea, an increase in SBP and DBP and a decrease in HR were observed in both SFM and CTL. At baseline, [AD]b was higher in SFM compared with CTL (1.05 ± 0.2 vs. 0.73 ± 0.11 μM, p &lt; 0.01). [AD]b increased significantly at the end of the apnea in both groups, but the increase was significantly greater in SFM than in controls (+90.4 vs. +12%, p &lt; 0.01). Importantly, in SFM, we also observed significant correlations between [AD]b and HR ( R = −0.8, p = 0.02), SpO 2 ( R = −0.69, p = 0.01), SBP ( R = −0.89, p = 0.02), and DBP ( R = −0.68, p = 0.03). Such associations were absent in CTL. The adenosine release during apnea was associated with blood O 2 saturation and cardiovascular parameters in trained divers but not in controls. These data therefore suggest that adenosine may play a major role in the adaptive cardiovascular response to apnea and could reflect the level of training

Hyperoxia During Exercise: Impact on Adenosine Plasma Levels and Hemodynamic Data

International audienceIntroduction: Adenosine is an ATP derivative that is strongly implicated in the cardiovascular adaptive response to exercise. In this study, we hypothesized that during exercise the hyperemia, commonly observed during exercise in air, was counteracted by the downregulation of the adenosinergic pathway during hyperoxic exposure. Methods: Ten healthy volunteers performed two randomized sessions including gas exposure (Medical air or Oxygen) at rest and during exercise performed at 40% of maximal intensity, according to the individual fitness of the volunteers. Investigations included the measurement of adenosine plasma level (APL) and the recording of hemodynamic data [i.e., cardiac output (CO) and systemic vascular resistances (SVR) using pulsed Doppler and echocardiography]. Results: Hyperoxia significantly decreased APL (from 0.58 ± 0.06 to 0.21 ± 0.05 µmol L −1 , p < 0.001) heart rate and CO and increased SVR in healthy volunteers at rest. During exercise, an increase in APL was recorded in the two sessions when compared with measurements at rest (+0.4 ± 0.4 vs. +0.3 ± 0.2 µmol L −1 for medical air and oxygen exposures, respectively). APL was lower during the exercise performed under hyperoxia when compared with medical air exposure (0.5 ± 0.06 vs. 1.03 ± 0.2 µmol L −1 , respectively p < 0.001). This result could contribute to the hemodynamic differences between the two conditions, such as the increase in SVR and the decrease in both heart rate and CO when exercises were performed during oxygen exposure as compared to medical air. Conclusion: Hyperoxia decreased APLs in healthy volunteers at rest but did not eliminate the increase in APL and the decrease in SVR during low intensity exercise

Hyperhomocysteinemia and Cardiovascular Disease: Is the Adenosinergic System the Missing Link?

International audienceThe influence of hyperhomocysteinemia (HHCy) on cardiovascular disease (CVD) remains unclear. HHCy is associated with inflammation and atherosclerosis, and it is an independent risk factor for CVD, stroke and myocardial infarction. However, homocysteine (HCy)-lowering therapy does not affect the inflammatory state of CVD patients, and it has little influence on cardiovascular risk. The HCy degradation product hydrogen sulfide (H2S) is a cardioprotector. Previous research proposed a positive role of H2S in the cardiovascular system, and we discuss some recent data suggesting that HHCy worsens CVD by increasing the production of H2S, which decreases the expression of adenosine A2A receptors on the surface of immune and cardiovascular cells to cause inflammation and ischemia, respectively

Predict Score: A New Biological and Clinical Tool to Help Predict Risk of Intensive Care Transfer for COVID-19 Patients

International audienceBackground: The COVID-19 crisis has strained world health care systems. This study aimed to develop an innovative prediction score using clinical and biological parameters (PREDICT score) to anticipate the need of intensive care of COVID-19 patients already hospitalized in standard medical units. Methods: PREDICT score was based on a training cohort and a validation cohort retrospectively recruited in 2020 in the Marseille University Hospital. Multivariate analyses were performed, including clinical, and biological parameters, comparing a baseline group composed of COVID-19 patients exclusively treated in standard medical units to COVID-19 patients that needed intensive care during their hospitalization. Results: Independent variables included in the PREDICT score were: age, Body Mass Index, Respiratory Rate, oxygen saturation, C-reactive protein, neutrophil–lymphocyte ratio and lactate dehydrogenase. The PREDICT score was able to correctly identify more than 83% of patients that needed intensive care after at least 1 day of standard medical hospitalization. Conclusions: The PREDICT score is a powerful tool for anticipating the intensive care need for COVID-19 patients already hospitalized in a standard medical unit. It shows limitations for patients who immediately need intensive care, but it draws attention to patients who have an important risk of needing intensive care after at least one day of hospitalization

Physiological stress markers during breath‐hold diving and SCUBA diving

Abstract This study investigated the sources of physiological stress in diving by comparing SCUBA dives (stressors: hydrostatic pressure, cold, and hyperoxia), apneic dives (hydrostatic pressure, cold, physical activity, hypoxia), and dry static apnea (hypoxia only). We hypothesized that despite the hypoxia induces by a long static apnea, it would be less stressful than SCUBA dive or apneic dives since the latter combined high pressure, physical activity, and cold exposure. Blood samples were collected from 12SCUBA and 12 apnea divers before and after dives. On a different occasion, samples were collected from the apneic group before and after a maximal static dry apnea. We measured changes in levels of the stress hormones cortisol and copeptin in each situation. To identify localized effects of the stress, we measured levels of the cardiac injury markers troponin (cTnI) and brain natriuretic peptide (BNP), the muscular stress markers myoglobin and lactate), and the hypoxemia marker ischemia‐modified albumin (IMA). Copeptin, cortisol, and IMA levels increased for the apneic dive and the static dry apnea, whereas they decreased for the SCUBA dive. Troponin, BNP, and myoglobin levels increased for the apneic dive, but were unchanged for the SCUBA dive and the static dry apnea. We conclude that hypoxia induced by apnea is the dominant trigger for the release of stress hormones and cardiac injury markers, whereas cold or and hyperbaric exposures play a minor role. These results indicate that subjects should be screened carefully for pre‐existing cardiac diseases before undertaking significant apneic maneuvers