BackgroundThe rapid and reliable exclusion of myocardial revascularization is a major unmet clinical need in patients with suspected coronary artery disease (CAD) and non‐contributive electrocardiography and troponin. Non‐invasive tests have high rates of false positives and negatives, and there is no biomarker to assess myocardial ischemia. The presence of spare adenosine A2A receptors (A2 AR)—characterized by a high dissociation constant/half maximal effective concentration (KD/EC 50) ratio—expressed on peripheral blood mononuclear cells (PBMC) has been associated with ischemia during exercise stress testing in patients with CAD. In this work, we investigated the diagnostic accuracy of spare A2 AR versus fractional flow reserve (FFR) in patients with suspected CAD.Methods and ResultsSixty patients with suspected CAD, but non‐contributive electrocardiography and troponin, were consecutively enrolled in this prospective study. The binding (KD), functional response (cyclic adenosine monophosphate [cAMP] production; EC 50) on PBMC A2 AR were compared with FFR results. Patients were divided into 3 groups: 17 (group 1) with normal coronary angiography (n=13) or stenosis <20% (n=4); 21 with CAD and non‐significant FFR (group 2); and 22 with CAD and significant FFR (group 3). Median KD/EC 50 was 6‐fold higher in group 3 (4.20; interquartile range: 2.81–5.00) than group 2 (0.66; interquartile range: 0.47–1.25) and 7‐fold higher than group 1 (0.60; interquartile range: 0.30–0.66).ConclusionsIn patients with suspected CAD and non‐contributive electrocardiography and troponin, the absence of spare A2 AR on PBMC may help to rule out myocardial ischemia.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03218007.

The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI < 1.67. We identified a linear correlation between SUA and RHI (R = 0.66 P < 0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients.

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&gt;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.

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.

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 12 SCUBA 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.

Electrolyte concentration in sweat depends on environmental context and physical condition but also on the pathophysiological status. Sweat analyzers may be therefore the future way for biological survey although how sweat electrolyte composition can reflect plasma composition remains unclear. We recruited 10 healthy subjects and 6 patients to have a broad range of plasma electrolyte concentrations (chloride, potassium and sodium) and pH. These variables were compared to those found in sweat produced following cycling exercise or pilocarpine iontophoresis, a condition compatible with operating a wearable device. We found no correlation between plasma and sweat parameters when exercise-induced sweat was analyzed, and we could identify a correlation only between plasma and sweat potassium concentration (R = 0.78, p < 0.01) when sweat was induced using pilocarpine iontophoresis. We tested measurement repeatability in sweat at 24hr-interval for 3 days in 4 subjects and found a great intra-individual variability regarding all parameters in exercise-induced sweat whereas similar electrolyte levels were measured in pilocarpine-induced sweat. Thus, electrolyte concentration in sweat sampled following physical activity does not reflect concentration in plasma while pilocarpine iontophoresis appears to be promising to reproducibly address sweat electrolytes, and to make an indirect evaluation of plasma potassium concentration in chronic kidney disease and arrhythmia.

BackgroundAltered 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. MethodsArtery 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 antibody with agonist properties, allowing determination of A2AR affinity (KD) and cAMP production (ie.EC50). Results A2AR expression onPBMCs was lower in patients than controls (median1.3 [range 0.6-1.8]vs1.75 [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]vs244 [110-380]pg/10 6 cells (P<0.05) and 375 [160-659]vs670 [410-980]pg/10 6 cells (P<0.05), respectively. A high KD/EC50 ratio, characteristic of spare receptors, was observed in CAD with inducible-myocardial-ischemia. ConclusionA2AR 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.

Background: Adenosine is a nucleoside that impacts the cardiovascular system during cardiovascular or inflammatory diseases. The rapid determination of adenosine in blood may be useful in emergency medicine especially in syncope diagnose or septic shock. We compare its measurement in blood using fixed potential amperometry (FPA), with usual methods: mass spectrometry (LC-MS/MS) or high performance liquid chromatography (HPLC). Methods:Twenty healthy subjects (14 men and 6 women) and ten patients suffering from vasovagal syncope (VVS, 6 women and 4 men) were included. Blood samples were collected by vein puncture for plasma adenosine assay and in the same time using finger puncture for direct FAP measurement and on blotting paper for LC-MS/MS. Results:Mean plasma adenosine concentration was 26% higher using HPLC compared with LC-MSMS; p<0.01. In whole blood, adenosine concentration was 35% higher using FPA compared with LC-MS/MS. We found a good correlation between adenosine values measured by FAP and LC-MS/MS in whole blood and between LC-MS/MS and HPLC in plasma. Mean adenosine concentration was higher in patients whatever the method used. Conclusion:Adenosine measurement to the patient's bed, using FPA may be useful in some cases where high adenosine is associated with pejorative outcome.