Objectives This study aimed to investigate the impact of ticagrelor on adenosine plasma concentration (APC) in acute coronary syndrome (ACS) patients. Background Ticagrelor is a direct-acting P2Y12 ...-adenosine diphosphate receptor blocker. The clinical benefit of ticagrelor compared with clopidogrel in ACS patients suggests that the drug has non–platelet-directed properties. Animal and in vitro models suggested that the “pleiotropic” properties of ticagrelor may be related to an interaction with adenosine metabolism. Methods We prospectively randomized 60 ACS patients to receive ticagrelor or clopidogrel. The APC was measured by liquid chromatography. To assess the mechanism of APC variation, we measured adenosine deaminase concentration, adenosine uptake by red blood cells, and cyclic adenosine monophosphate production by cells overexpressing adenosine receptors. The P2Y12 -adenosine diphosphate receptor blockade was assessed by the vasodilator-stimulated phosphoprotein index. Results Patients receiving ticagrelor had significantly higher APC than patients receiving clopidogrel (1.5 μM interquartile range: 0.98 to 1.7 μM vs. 0.68 μM interquartile range: 0.49 to 0.78 μM; p < 0.01). The APC was not correlated with vasodilator-stimulated phosphoprotein (p = 0.16). Serum-containing ticagrelor inhibited adenosine uptake by red blood cells compared with clopidogrel or controls (p < 0.01 for both comparisons). Adenosine deaminase activity was similar in serum of patients receiving clopidogrel or ticagrelor (p = 0.1). Ticagrelor and clopidogrel had no direct impact on adenosine receptors (p = not significant). Conclusions Ticagrelor increases APC in ACS patients compared with clopidogrel by inhibiting adenosine uptake by red blood cells.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), altered membrane excitability often occurs in exercising muscles demonstrating muscle dysfunction regardless of any psychiatric ...disorder. Increased oxidative stress is also present in many ME/CFS patients and could affect the membrane excitability of resting muscles.
Seventy-two patients were examined at rest, during an incremental cycling exercise and during a 10-min post-exercise recovery period. All patients had at least four criteria leading to a diagnosis of ME/CFS. To explore muscle membrane excitability, M-waves were recorded during exercise (rectus femoris (RF) muscle) and at rest (flexor digitorum longus (FDL) muscle). Two plasma markers of oxidative stress (thiobarbituric acid reactive substance (TBARS) and oxidation-reduction potential (ORP)) were measured. Plasma potassium (K
) concentration was also measured at rest and at the end of exercise to explore K
outflow.
Thirty-nine patients had marked M-wave alterations in both the RF and FDL muscles during and after exercise while the resting values of plasma TBARS and ORP were increased and exercise-induced K
outflow was decreased. In contrast, 33 other patients with a diagnosis of ME/CFS had no M-wave alterations and had lower baseline levels of TBARS and ORP. M-wave changes were inversely proportional to TBARS and ORP levels.
Resting muscles of ME/CFS patients have altered muscle membrane excitability. However, our data reveal heterogeneity in some major biomarkers in ME/CFS patients. Measurement of ORP may help to improve the diagnosis of ME/CFS. Trial registration Ethics Committee "Ouest II" of Angers (May 17, 2019) RCB ID: number 2019-A00611-56.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Central or peripheral baroreceptor reflex abnormalities, alterations in neurohumoral mechanisms, or both, are thought to play a role in causing neurally-mediated syncope. Because adenosine and its ...receptors are involved in some forms of syncope (1-3), we evaluated the purinergic profile of 4 common forms of syncope: typical vasovagal syncope (VVS); situational syncope (which occurs in specific circumstances after micturition, defecation, coughing, swallowing, or gastrointestinal stimulation); carotid sinus syncope (CSS); and syncope without prodromes or with very short (2 to 3 s) prodromes and a normal heart (no prodromes). Clinical and biological characteristics of patients and control subjects are given in Table 1. ...these findings demonstrate an association between adenosine plasmatic levels and unexplained syncope in patients without prodromes, CSS, and VVS, who have profiles different from normal control subjects.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives This study sought to investigate the clinical and laboratory findings of patients affected by sudden-onset syncope without prodromes who had a normal heart and normal electrocardiogram. ...Background The pathophysiology of syncope in these patients is uncertain. Methods We compared the clinical and laboratory findings of 15 patients with sudden-onset syncope without prodromes who had a normal heart and normal electrocardiogram (the study group) with those of 31 patients with established vasovagal syncope (VVS). Results The patients in the study group were older than those with VVS (age 61 ± 12 years vs. 46 ± 17 years) and had a history of fewer episodes of syncope (median of 2 interquartile range IQR: 1 to 2.5 vs. 9 IQR: 4 to 15 years) that were of more recent onset (median of 1 IQR: 0 to 1 vs. 10.5 IQR: 3.3 to 27 years). The study group had lower median baseline adenosine plasmatic levels than the VVS group (0.25 μmol/l 95% confidence interval: 0.10 to 1.51 vs. 0.85 μmol/l 95% confidence interval: 0.32 to 2.80). On receiver-operating characteristic curve analysis, the adenosine plasmatic level of ≤0.36 best discriminated between groups, displaying 73% sensitivity and 93% specificity. Tilt table testing was more frequently positive in patients with VVS than in the study group (74% vs. 33%). A similarly high positivity rate of adenosine/adenosine triphosphate testing was found in both groups. Conclusions Common clinical features and a low adenosine plasmatic level define a distinct form of syncope, distinguish it from VVS, and suggest a causal role of the adenosine pathway.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
The 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 (A2AR)—characterized by a high dissociation constant/half maximal effective concentration (KD/EC50) 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 A2AR versus fractional flow reserve (FFR) in patients with suspected CAD.
Methods and Results
Sixty 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; EC50) on PBMC A2AR 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/EC50 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).
Conclusions
In patients with suspected CAD and non‐contributive electrocardiography and troponin, the absence of spare A2AR on PBMC may help to rule out myocardial ischemia.
Clinical Trial Registration
URL: http://www.clinicaltrials.gov. Unique identifier: NCT03218007.
The nucleoside adenosine acts on the nervous and cardiovascular systems via the A2A receptor (A2AR). In response to oxygen level in tissues, adenosine plasma concentration is regulated in particular ...via its synthesis by CD73 and via its degradation by adenosine deaminase (ADA). The cell-surface endopeptidase CD26 controls the concentration of vasoactive and antioxidant peptides and hence regulates the oxygen supply to tissues and oxidative stress response. Although overexpression of adenosine, CD73, ADA, A2AR, and CD26 in response to hypoxia is well documented, the effects of hyperoxic and hyperbaric conditions on these elements deserve further consideration. Rats and a murine Chem-3 cell line that expresses A2AR were exposed to 0.21 bar O2, 0.79 bar N2 (terrestrial conditions; normoxia); 1 bar O2 (hyperoxia); 2 bar O2 (hyperbaric hyperoxia); 0.21 bar O2, 1.79 bar N2 (hyperbaria). Adenosine plasma concentration, CD73, ADA, A2AR expression, and CD26 activity were addressed in vivo, and cAMP production was addressed in cellulo. For in vivo conditions, 1) hyperoxia decreased adenosine plasma level and T cell surface CD26 activity, whereas it increased CD73 expression and ADA level; 2) hyperbaric hyperoxia tended to amplify the trend; and 3) hyperbaria alone lacked significant influence on these parameters. In the brain and in cellulo, 1) hyperoxia decreased A2AR expression; 2) hyperbaric hyperoxia amplified the trend; and 3) hyperbaria alone exhibited the strongest effect. We found a similar pattern regarding both A2AR mRNA synthesis in the brain and cAMP production in Chem-3 cells. Thus a high oxygen level tended to downregulate the adenosinergic pathway and CD26 activity. Hyperbaria alone affected only A2AR expression and cAMP production. We discuss how such mechanisms triggered by hyperoxygenation can limit, through vasoconstriction, the oxygen supply to tissues and the production of reactive oxygen species.
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.
PDF
