Mortality, cardiac and cerebral damages reduction by IL-1 inhibition in a murine model of TTP.

Thrombotic thrombocytopenic purpura (TTP), a rare but fatal disease if untreated, is due to alteration in Von Willebrand factor cleavage resulting in capillary microthrombi formation and ischemic organ damage. Interleukin-1 (IL-1), has been shown to drive sterile inflammation following ischemia and could play an essential contribution to post-ischemic organ damage in TTP. Our objectives were to evaluate IL-1 involvement during TTP and to test the efficacy of the recombinant IL-1 receptor antagonist, anakinra, in a murine TTP model. We retrospectively measured plasmatic IL-1 concentrations in TTP patients and controls. TTP patients exhibited elevated plasma IL-1α and ß concentrations, which correlated with disease course and survival. In a TTP mouse model, we administered anakinra (IL-1 inhibitor) or placebo for 5 days and evaluated the efficacy of this treatment. Anakinra significantly reduced mortality of mice (P<0.001). Anakinra significantly decreased TTP-induced cardiac damages as assessed by blood troponin concentrations, evaluation of left ventricular function by echocardiography, [18F]FDG PET of myocardial glucose metabolism, and cardiac histology. Anakinra also significantly reduced brain TTP-induced damages, evaluated through blood PS100b concentrations, nuclear imaging and histology. We finally showed that IL-1α and ß trigger endothelial degranulation in vitro, leading to the release of Von Willebrand factor. In conclusion, Anakinra significantly reduced TTP mortality in a pre-clinical model of the disease by inhibiting both endothelial degranulation and post-ischemic inflammation, supporting further evaluations in humans.

Low Density Lipoprotein Cholesterol Decreases the Expression of Adenosine A2A Receptor and Lipid Rafts-Protein Flotillin-1: Insights on Cardiovascular Risk of Hypercholesterolemia.

High blood levels of low-density lipoprotein (LDL)-cholesterol (LDL-C) are associated with atherosclerosis, mainly by promoting foam cell accumulation in vessels. As cholesterol is an essential component of cell plasma membranes and a regulator of several signaling pathways, LDL-C excess may have wider cardiovascular toxicity. We examined, in untreated hypercholesterolemia (HC) patients, selected regardless of the cause of LDL-C accumulation, and in healthy participants (HP), the expression of the adenosine A2A receptor (A2AR), an anti-inflammatory and vasodilatory protein with cholesterol-dependent modulation, and Flotillin-1, protein marker of cholesterol-enriched plasma membrane domains. Blood cardiovascular risk and inflammatory biomarkers were measured. A2AR and Flotillin-1 expression in peripheral blood mononuclear cells (PBMC) was lower in patients compared to HP and negatively correlated to LDL-C blood levels. No other differences were observed between the two groups apart from transferrin and ferritin concentrations. A2AR and Flotillin-1 proteins levels were positively correlated in the whole study population. Incubation of HP PBMCs with LDL-C caused a similar reduction in A2AR and Flotillin-1 expression. We suggest that LDL-C affects A2AR expression by impacting cholesterol-enriched membrane microdomains. Our results provide new insights into the molecular mechanisms underlying cholesterol toxicity, and may have important clinical implication for assessment and treatment of cardiovascular risk in HC.

Adenosinergic System and Neuroendocrine Syncope: What Is the Link?

Although very common, the precise mechanisms that explain the symptomatology of neuroendocrine syncope (NES) remain poorly understood. This disease, which can be very incapacitating, manifests itself as a drop in blood pressure secondary to vasodilation and/or extreme slowing of heart rate. As studies continue, the involvement of the adenosinergic system is becoming increasingly evident. Adenosine, which is an ATP derivative, may be involved in a large number of cases. Adenosine acts on G protein-coupled receptors with seven transmembrane domains. A1 and A2A adenosine receptor dysfunction seem to be particularly implicated since the activation leads to severe bradycardia or vasodilation, respectively, two cardinal symptoms of NES. This mini-review aims to shed light on the links between dysfunction of the adenosinergic system and NHS. In particular, signal transduction pathways through the modulation of cAMP production and ion channels in relation to effects on the cardiovascular system are addressed. A better understanding of these mechanisms could guide the pharmacological development of new therapeutic approaches.

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in the world. Because the key to developing innovative therapies that limit the onset and the progression of AF is to fully understand the underlying molecular mechanisms of AF, the aim of the present narrative review is to report the most recent advances in the potential role of the adenosinergic system in the pathophysiology of AF. After a comprehensive approach describing adenosinergic system signaling and the mechanisms of the initiation and maintenance of AF, we address the interactions of the adenosinergic system's signaling with AF. Indeed, adenosine release can activate four G-coupled membrane receptors, named A1, A2A, A2B and A3. Activation of the A2A receptors can promote the occurrence of delayed depolarization, while activation of the A1 receptors can shorten the action potential's duration and induce the resting membrane's potential hyperpolarization, which promote pulmonary vein firing, stabilize the AF rotors and allow for functional reentry. Moreover, the A2B receptors have been associated with atrial fibrosis homeostasis. Finally, the adenosinergic system can modulate the autonomous nervous system and is associated with AF risk factors. A question remains regarding adenosine release and the adenosine receptors' activation and whether this would be a cause or consequence of AF.

Adenosine Receptors Profile in Fibromuscular Dysplasia.

Fibromuscular dysplasia (FMD) is a non-inflammatory vascular disease that is characterized by unexplained systemic hypertension occurring in young people, associated with arterial stenosis, aneurysm rupture, intracranial/renal infarction, and stroke. Although the gold standard for the diagnosis remains catheter-angiography, biological markers would be helpful due to the delay from first symptom to diagnosis. Adenosine is an ATP derivative, that may be implicated in FMD pathophysiology. We hypothesized that changes in adenosine blood level (ABL) and production of adenosine receptors may be associated with FMD. Using peripheral blood mononuclear cells, we evaluated A1, A2A, and A2B receptor production by Western blot, in 67 patients (17 men and 50 women, mean (range) age 55 (29−77) years and 40 controls, 10 men and 30 women, mean (range) age 56 (37−70)). ABL was evaluated by liquid chromatography, mass spectrometry. ABL was significantly higher in patients vs. controls, mean (range): 1.7 (0.7−3) µmol/L vs. controls 0.6 (0.4−0.8) µmol/L (+180%) p < 0.001. While A1R and A2AR production did not differ in patients and controls, we found an over-production of A2BR in patients: 1.70 (0.90−2.40; arbitrary units) vs. controls = 1.03 (0.70−1.40), mean + 65% (p < 0.001). A2BR production with a cut off of 1.3 arbitrary units, gives a good sensitivity and specificity for the diagnosis. Production measurement of A2BR on monocytes and ABL could help in the diagnosis, especially in atypical or with poor symptoms.

Plasma A2AR Measurement Can Help Physicians Identify Patients Suspected of Coronary Chronic Syndrome: A Pilot Study.

The evaluation of suspected coronary artery disease (CAD) in the medical community is challenging. Patients with suspected coronary chronic syndrome (CCS) are referred by the medical community to be assessed by specialists for the performance of noninvasive tests that have high rates of false positives and false negatives. While troponins are the gold standard for evaluate myocardial injuries, there is no biomarker to assess myocardial ischemia in patient populations with negative electrocardiography or without an increase in troponin level. A2A adenosine receptors control the coronary blood flow through its vasodilating properties. It has been shown that patients with CAD have a lower A2AR expression on peripheral blood mononuclear cells, suggesting a link between A2AR production and the severity of CAD. Herein, we present a new and innovative method of inhibition ELISA for A2AR in the plasma of patients who permit the evaluation of the amount of soluble A2AR. For this analysis, the total study sample was 54, including 31 patients with CAD with stenosis > 50% and a significant fractional flow reserve (FFR < 0.8) (Group 1) and 23 patients with normal or non-obstructive coronary arteries (stenosis < 50% and nonsignificant FFR > 0.8) (Group 2). The % inhibition (which is linked to the presence of soluble receptors) with the plasma of patients with FFR < 0.8 was significantly lower than that of patients with FFR > 0.8 (median [range]: 68% [20.7−86.9] vs. 83% [67−88.4]; p < 0.001). The ROC curve indicated a good sensitivity/specificity ratio with a cut off of 72.5% and an area under the curve of 0.87. In conclusion, a rapid ELISA to assess soluble A2AR in the plasma shows promise to screen patients suspected of having CAD.

A2 Adenosine Receptor Subtypes Overproduction in Atria of Perioperative Atrial Fibrillation Patients Undergoing Cardiac Surgery: A Pilot Study.

Objective: Although atrial fibrillation is a common cardiac arrhythmia in humans, the mechanism that leads to the onset of this condition is poorly elucidated. Adenosine is suspected to be implicated in the trigger of atrial fibrillation (AF) through the activation of its membrane receptors, mainly adenosine receptor (AR) subtypes A1R and A2R. In this study, we compared blood adenosine concentration (BAC), and A1R, A2AR, and A2BR production in right (RA) and left atrium (LA), and on peripheral blood mononuclear cells (PBMCs) in patients with underlying structural heart disease undergoing cardiac surgery with or without peri-operative AF (PeOpAF). Methods: The study group consisted of 39 patients (30 men and 9 women, mean age, range 65 [40-82] years) undergoing cardiac surgery and 20 healthy patients (8 women and 12 men; mean age, range 60 [39-72] years) as controls were included. Among patients, 15 exhibited PeOpAF. Results: Blood adenosine concentration was higher in patients with PeOpAF than others. A2AR and A2BR production was higher in PBMCs of patients compared with controls and was higher in PeOpAF patients than other patients. In LA and RA, the production of A2AR and A2BR was higher in patients with PeOpAF than in other patients. Both A2AR and A2BR production were higher in LA vs. RA. A1R production was unchanged in all situations. Finally, we observed a correlation between A1R, A2AR, and A2BR production evaluated on PBMCs and those evaluated in LA and RA. Conclusions: Perioperative AF was associated with high BAC and high A2AR and A2BR expression, especially in the LA, after cardiac surgery in patients with underlying structural heart disease. Whether these increases the favor in triggering the AF in this patient population needs further investigation.

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

The 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 < 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 < 0.01). Importantly, in SFM, we also observed significant correlations between [AD]b and HR (R = -0.8, p = 0.02), SpO2 (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 O2 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.

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

BACKGROUND: 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.

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

The 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.

Adenosine and Its Receptors: An Expected Tool for the Diagnosis and Treatment of Coronary Artery and Ischemic Heart Diseases.

Adenosine is an endogenous nucleoside which strongly impacts the cardiovascular system. Adenosine is released mostly by endothelial cells and myocytes during ischemia or hypoxia and greatly regulates the cardiovascular system via four specific G-protein-coupled receptors named A1R, A2AR, A2BR, and A3R. Among them, A2 subtypes are strongly expressed in coronary tissues, and their activation increases coronary blood flow via the production of cAMP in smooth muscle cells. A2A receptor modulators are an opportunity for intense research by the pharmaceutical industry to develop new cardiovascular therapies. Most innovative therapies are mediated by the modulation of adenosine release and/or the activation of the A2A receptor subtypes. This review aims to focus on the specific exploration of the adenosine plasma level and its relationship with the A2A receptor, which seems a promising biomarker for a diagnostic and/or a therapeutic tool for the screening and management of coronary artery disease. Finally, a recent class of selective adenosine receptor ligands has emerged, and A2A receptor agonists/antagonists are useful tools to improve the management of patients suffering from coronary artery disease.

Homocysteine concentration and adenosine A2A receptor production by peripheral blood mononuclear cells in coronary artery disease patients.

Hyperhomocysteinemia is associated with coronary artery disease (CAD). The mechanistic aspects of this relationship are unclear. In CAD patients, homocysteine (HCy) concentration correlates with plasma level of adenosine that controls the coronary circulation via the activation of adenosine A2A receptors (A2A R). We addressed in CAD patients the relationship between HCy and A2A R production, and in cellulo the effect of HCy on A2A R function. 46 patients with CAD and 20 control healthy subjects were included. We evaluated A2A R production by peripheral blood mononuclear cells using Western blotting. We studied in cellulo (CEM human T cells) the effect of HCy on A2A R production as well as on basal and stimulated cAMP production following A2A R activation by an agonist-like monoclonal antibody. HCy concentration was higher in CAD patients vs controls (median, range: 16.6 [7-45] vs 8 [5-12] µM, P < 0.001). A2A R production was lower in patients vs controls (1.1[0.62-1.6] vs 1.53[0.7-1.9] arbitrary units, P < 0.001). We observed a negative correlation between HCy concentration and A2A R production (r = -0.43; P < 0.0001), with decreased A2A R production above 25 µM HCy. In cellulo, HCy inhibited A2A R production, as well as basal and stimulated cAMP production. In conclusion, HCy is negatively associated with A2A R production in CAD patients, as well as with A2A R and cAMP production in cellulo. The decrease in A2A R production and function, which is known to hamper coronary blood flow and promote inflammation, may support CAD pathogenesis.

Plasma adenosine and neurally mediated syncope: ready for clinical use.

Either central or peripheral baroreceptor reflex abnormalities and/or alterations in neurohumoral mechanisms play a pivotal role in the genesis of neurally mediated syncope. Thus, improving our knowledge of the biochemical mechanisms underlying specific forms of neurally mediated syncope (more properly termed 'neurohumoral syncope') might allow the development of new therapies that are effective in this specific subgroup. A low-adenosine phenotype of neurohumoral syncope has recently been identified. Patients who suffer syncope without prodromes and have a normal heart display a purinergic profile which is the opposite of that observed in vasovagal syncope patients and is characterized by very low-adenosine plasma level values, low expression of A2A receptors and the predominance of the TC variant in the single nucleotide c.1364 C>T polymorphism of the A2A receptor gene. The typical mechanism of syncope is an idiopathic paroxysmal atrioventricular block or sinus bradycardia, most often followed by sinus arrest. Since patients with low plasma adenosine levels are highly susceptible to endogenous adenosine, chronic treatment of these patients with theophylline, a non-selective adenosine receptor antagonist, is expected to prevent syncopal recurrences. This hypothesis is supported by results from series of cases and from observational controlled studies.

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

INTRODUCTION: 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.

Physiological stress markers during breath-hold diving and SCUBA diving.

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.

Pharmacological profile of adenosine A2A receptors in patients with lower extremity peripheral artery disease and associated coronary artery disease: A pilot study.

BACKGROUND: Altered blood flow occurs in patients with low extremity peripheral artery disease (LE-PAD). LE-PAD is mostly associated with coronary artery disease (CAD). Adenosine is an endogenous nucleoside that affects both coronary and limb artery blood flow, mostly via the adenosine A2A receptor (A2AR). We evaluated A2AR expression and function in peripheral blood mononuclear cells (PBMCs) and the femoral artery tissues of patients with LE-PAD. METHODS: Artery tissues and PBMCs were sampled in 24 patients with intermittent claudication, and compared with PBMCs in 24 healthy subjects. Expression and function of A2AR was studied, using a A2AR monoclonal antibody with agonist properties, allowing determination of A2AR affinity (KD) and cAMP production (ie.EC50). RESULTS: A2AR expression on PBMCs was lower in patients than controls (median1.3 [range 0.6-1.8] vs 1.75 [1.45-2.1] arbitrary units; P < 0.01), and correlated with A2AR expression in artery tissues (Pearson's r = 0.71; P < 0.01). Basal and maximally stimulated cAMP production of PBMCs was lower in patients vs controls: 172 [90-310] vs 244 [110-380] pg/106 cells (P < 0.05) and 375 [160-659] vs 670 [410-980] pg/106 cells (P < 0.05), respectively. A high KD/EC50 ratio, characteristic of spare receptors, was observed in CAD with inducible-myocardial-ischemia. CONCLUSION: A2AR expression in the arteries of patients, correlated with their expression in PBMCs. A2AR expression was lower in patients than in controls. A single blood sample (for measurement of A2AR expression on PBMCs) may help to screen patients with LE-PAD, whereas the presence of spare receptors may help with risk stratification before vascular surgery in CAD patients with high risk of myocardial ischemia.

Adenosine plasma level in patients with paroxysmal or persistent atrial fibrillation and normal heart during ablation procedure and/or cardioversion.

The mechanism of atrial fibrillation (AF) in patients with normal heart remains unclear. While exogenous adenosine can trigger AF, nothing is known about the behavior of endogenous adenosine plasma level (APL) at the onset of AF and during ablation procedure. Ninety-one patients (68 with paroxysmal AF: 40 males, 66 ± 16 years; 23 with persistent AF: 14 males, 69 ± 11 years) and 18 controls were included. Among paroxysmal patients: i) medical therapy alone was performed in 45 cases and ablation procedure in 23. AF was spontaneously resolutive in 6 cases; ii) 23 underwent ablation procedure and blood was collected simultaneously in a brachial vein and in the left atrium; 17 were spontaneously in sinus rhythm while 6 were in sinus rhythm after direct current cardioversion. Among persistent patients: i) in 17 patients, blood samples were collected in a brachial vein before and after direct current cardioversion; ii) in 6 patients, blood samples were collected simultaneously in a brachial vein and in left atrium before and after cardioversion during ablation procedure. CV-APL was higher in patients with persistent AF vs patients with paroxysmal AF (median [range]: 0.9[0.6-1.1] vs 0.7[0.4-1.1] µM; p < 0.001). In patients with paroxysmal AF, LA-APL increased during the AF episode (0.95[0.85-1.4] vs 2.7[1.5-7] µM; p = 0.03) and normalized in sinus rhythm after DCCV. In patients with persistent AF, LA-APL was higher than CV-APL (1.2[0.7-1.8] vs 0.9[0.6-1.1] µM; p < 0.001), and both normalized in sinus rhythm (CV-APL: 0.8[0.6-1.1] vs 0.75[0.4-1] µM; p = 0.03), (LA-APL: 1.95[1.3-3] vs 1[0.5-1.15] µM; p = 0.03). The occurrence of AF is associated with a strong increase of APL in the atrium. The cause of this increase needs further investigations.

Troponins in scuba divers with immersion pulmonary edema.

Immersion pulmonary edema (IPE) is a serious complication of water immersion during scuba diving. Myocardial ischemia can occur during IPE that worsens outcome. Because myocardial injury impacts the therapeutic management, we aim to evaluate the profile of cardiac markers (creatine phosphokinase (CPK), brain natriuretic peptide (BNP), highly sensitive troponin T (TnT-hs) and ultrasensitive troponin I (TnI-us) of divers with IPE. Twelve male scuba divers admitted for suspected IPE were included. The collection of blood samples was performed at hospital entrance (T0) and 6 h later (T0 + 6 h). Diagnosis was confirmed by echocardiography or computed-tomography scan. Mean ± S.D. BNP (pg/ml) was 348 ± 324 at T0 and 223 ± 177 at T0 + 6 h (P<0.01), while mean CPK (international units (IUs)), and mean TnT-hs (pg/ml) increased in the same times 238 ± 200 compared with 545 ± 39, (P=0.008) and 128 ± 42 compared with 269 ± 210, (P=0.01), respectively; no significant change was observed concerning TnI-us (pg/ml): 110 ± 34 compared with 330 ± 77, P=0.12. At T0 + 6 h, three patients had high TnI-us, while six patients had high TnT-hs. Mean CPK was correlated with TnT-hs but not with TnI-us. Coronary angiographies were normal. The increase in TnT during IPE may be secondary to the release of troponin from non-cardiac origin. The measurement of TnI in place of TnT permits in some cases to avoid additional examinations, especially unnecessary invasive investigations.