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1.
J Cell Mol Med ; 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31444994

RESUMO

Extracellular vesicles (EV) can transfer cellular molecules for specific intercellular communication with potential relevance in pathological conditions. We searched for the presence in plasma from coronary artery disease (CAD) patients of EV containing the adenosine A2A receptor (A2A R), a signalling receptor associated with myocardial ischaemia and whose expression is related to homocysteine (HCy) metabolism. Using protein organic solvent precipitation for plasma EV preparation and Western blotting for protein identification, we found that plasma from CAD patients contained various amounts of EV with ubiquitin bound to A2A R. Interestingly, the presence of ubiquitinated A2A R in EV from patients was dependent on hyperhomocysteinemia, the amount being inversely proportional to A2A R expression in peripheral mononuclear cells in patients with the highest levels of HCy. CEM, a human T cell line, was also found to released EV containing various amounts of ubiquitinated A2A R in stimulated conditions depending on the hypoxic status and HCy level of culture medium. Together, these data show that ubiquitinated A2A R-containing EV circulate in the plasma of CAD patients and that this presence is related to hyperhomocysteinemia. A2A R in plasma EV could be a useful tool for diagnosis and a promising drug for the treatment of CAD.

2.
Int J Cardiol ; 289: 70-73, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30928258

RESUMO

BACKGROUND: Patients affected by syncope without or with very short (≤5 s) prodrome with normal heart and normal ECG have been seen to present low plasma adenosine levels. We investigated whether chronic treatment of these patients with theophylline, a non-selective adenosine receptor antagonist, results in clinical benefit. METHODS: In a consecutive case-series of 16 patients (mean age 47 ±â€¯25 years, 9 females) who had ECG documentation of asystolic syncope, we compared the incidence of syncopal recurrence during a period without and a period with tailored theophylline therapy. RESULTS: During a median of 60 months before ECG documentation of the index episode, the patients had a median of 2 syncopes per year. During the 6 months of the study phase without therapy, the patients had a median of 2.6 syncopes per year, p = 0.63. During the 23 months of the study phase with theophylline, the patients had a median of 0.4 syncopes per year, p = 0.005 vs history and p = 0.005 vs no therapy. In the 13 patients who had an implantable loop recorder during both study phases, the incidence of asystolic episodes > 3 s decreased from 9.6 per year to 1.1 per year, p = 0.0007. During theophylline treatment, syncope recurred in 1/5 (20%) patients who had an idiopathic atrioventricular block as the index event versus 9/11 (81%) patients who had a sinus arrest, p = 0.005. CONCLUSION: Theophylline is effective in reducing syncopal burden in patients with syncope without prodromes with normal heart and normal ECG. Its efficacy is greater in those with idiopathic atrioventricular block.

3.
Int J Cardiol ; 285: 121-127, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-30850237

RESUMO

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.

4.
5.
Physiol Rep ; 7(6): e14033, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30912280

RESUMO

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.

6.
Purinergic Signal ; 15(1): 45-52, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30535950

RESUMO

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.


Assuntos
Adenosina/sangue , Fibrilação Atrial/sangue , Idoso , Fibrilação Atrial/terapia , Ablação por Cateter , Cardioversão Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
7.
Biosci Rep ; 38(5)2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30201695

RESUMO

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.

8.
Crit Care Med ; 46(9): e874-e880, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29923934

RESUMO

OBJECTIVES: To investigate whether adenosine A2A receptors lead to vasodilation and positive inotropic function under stimulation and whether they play a role in the control of blood pressure in patients with cardiogenic shock. DESIGN: Prospective observational study. SETTING: Monocentric, Hopital Nord, Marseille, France. SUBJECTS: Patients with cardiogenic shock (n = 16), acute heart failure (n = 16), and acute myocardial infarction (n = 16). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial adenosine plasma level and A2A receptor expression on peripheral blood mononuclear cells were evaluated by mass spectrometry and Western blot, respectively, at admission and after 24 hours. Hemodynamic parameters, including systemic vascular resistance, were also assessed. Mean adenosine plasma level at admission was significantly higher in patients with cardiogenic shock (2.74 ± 1.03 µM) versus acute heart failure (1.33 ± 0.27) or acute myocardial infarction (1.19 ± 0.27) (normal range, 0.4-0.8 µM) (p < 0.0001). No significant correlation was found between adenosine plasma level and systemic vascular resistance. Mean adenosine plasma level decreased significantly by 24 hours after admission in patients with cardiogenic shock (2.74 ± 1.03 to 1.53 ± 0.68; p < 0.001). Mean A2A receptor expression was significantly lower in patients with cardiogenic shock (1.18 ± 0.11) versus acute heart failure (1.18 ± 0.11 vs 1.39 ± 0.08) (p = 0.005). CONCLUSIONS: We observed high adenosine plasma level and low A2A receptor expression at admission in patients with cardiogenic shock versus acute heart failure or acute myocardial infarction. This may contribute to the physiopathology of cardiogenic shock.

9.
Herzschrittmacherther Elektrophysiol ; 29(2): 166-170, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29845316

RESUMO

Adenosine is a ubiquitous substance that is released under several physiological and pathological conditions and has cardiovascular effects including cardioinhibition and vasodilation. It has been shown to be an important modulator implicated in several forms of syncope. In patients with chronic low plasma levels of adenosine, a transient release of endogenous adenosine can be sufficient to block conduction in the atrioventricular node and induce prolonged asystole; conversely, when plasma adenosine levels are chronically high, adenosine release is responsible for vasodepression. Distinct purinergic profiles in patients presenting with syncope have recently been correlated with the clinical presentation: "low-adenosine patients," prone to asystole, may present with idiopathic atrioventricular block, carotid sinus syndrome, or syncope with no or very brief prodromes and normal heart; "high-adenosine patients," prone to vasodilation, experience vasovagal syncope. This pathophysiological classification may have therapeutic implications.

10.
J Am Heart Assoc ; 7(8)2018 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-29654194

RESUMO

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.

11.
Purinergic Signal ; 14(2): 191-199, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29626320

RESUMO

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 (R2 = 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.

12.
Eur J Anaesthesiol ; 35(12): 911-918, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29702502

RESUMO

BACKGROUND: Raised plasma levels of endogenous adenosine after cardiac surgery using cardiopulmonary bypass (CPB) have been related to the incidence of postoperative atrial fibrillation (POAF). OBJECTIVE: We wished to assess if caffeine, an adenosine receptor antagonist could have a beneficial effect on the incidence of POAF. DESIGN: A randomised controlled study. SETTING: Single University Hospital. PATIENTS: One hundred and ten patients scheduled for heart valve surgery with CPB. INTERVENTIONS: We randomly assigned patients to receive peri-operative oral caffeine (400 mg every 8 h for 2 days) or placebo. Adenosine plasma concentrations and caffeine pharmacokinetic profile were evaluated in a subgroup of 50 patients. MAIN OUTCOME MEASURES: The primary endpoint was the rate of atrial fibrillation during postoperative hospital stay. RESULTS: The current study was stopped for futility by the data monitoring board after an interim analysis. The incidence of atrial fibrillation was similar in the caffeine and in the placebo group during hospital stay (33 vs. 29%, P = 0.67) and the first 3 postoperative days (18 vs. 15%; P = 0.60). Basal and postoperative adenosine plasma levels were significantly associated with the primary outcome. Adenosine plasma levels were similar in the two treatment groups. Caffeine administration was associated with a higher incidence of postoperative nausea and vomiting (27 vs. 7%, P = 0.005). CONCLUSION: Oral caffeine does not prevent POAF after heart valve surgery with CPB but increased the incidence of postoperative nausea and vomiting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, no.: NCT01999829.

14.
Toxicon ; 149: 72-85, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29337220

RESUMO

This work reports the purification of new potent scorpion neuropeptide, named BotAF, by an activity-guided screening approach. BotAF is a 64-residue long-chain peptide that shares very high similarity with the original ß-like scorpion toxin group, in which several peptides have been characterized to be anti-nociceptive in rodents. BotAF administration to rodents does not produce any toxicity or motor impairment, including at high doses. In all models investigated, BotAF turned out to be an efficient peptide in abolishing acute and inflammatory (both somatic and visceral) pain in rodents. It performs with high potency compared to standard analgesics tested in the same conditions. The anti-nociceptive activity of BotAF depends on the route of injection: it is inactive when tested by i.c.v. or i.v. routes but gains in potency when pre-injected locally (in the same compartment than the irritant itself) or by i.t. root 40 to 60 min before pain induction, respectively. BotAF is not an AINS-like compound as it fails to reduce inflammatory edema. Also, it does not activate the opioidergic system as its activity is not affected by naloxone. BotAF does also not bind onto RyR and has low activity towards DRG ion channels (particularly TTX sensitive Na+ channels) and does not bind onto rat brain synaptosome receptors. In somatic and visceral pain models, BotAF dose-dependently inhibited lumbar spinal cord c-fos/c-jun mRNA up regulation. Altogether, our data favor a spinal or peripheral anti-nociceptive mode of action of BotAF.


Assuntos
Analgésicos/farmacologia , Venenos de Escorpião/farmacologia , Escorpiões/química , Analgésicos/química , Analgésicos/toxicidade , Animais , Feminino , Masculino , Camundongos Endogâmicos C57BL , Dor/tratamento farmacológico , Ratos Wistar , Venenos de Escorpião/química , Venenos de Escorpião/toxicidade , Análise de Sequência de Proteína , Testes de Toxicidade
15.
Pacing Clin Electrophysiol ; 41(5): 444-446, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29148059

RESUMO

Early repolarization (ER) has been associated with an increased risk of sudden cardiac arrest. Interestingly, ventricular arrhythmias seem to be triggered by parasympathetic stimulation. In the present case report, we describe complete control of highly frequent malignant ventricular arrhythmias after adding theophylline to ineffective oral hydroquinidine and high-rate pacing in a patient suffering from malignant ER. We hypothesize that the theophylline-mediated enhanced beta-adrenergic stimulation could reduce the transmural myocardial voltage discrepancy by increasing the inward ICa,L current.

16.
Oncotarget ; 8(57): 97394-97406, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29228619

RESUMO

Background: Microparticles (MPs) are plasma membrane-derived extracellular vesicles present in the bloodstream. We have described a specific signature of MPs, called microparticulosome, in colorectal (CRC) and pancreatic (PC) cancers. We observed that levels of fibrin-bearing MPs were significantly increased in patients suffering from PC and CRC in comparison with control groups. Here, we hypothesised that fibrin-MPs may constitute a relevant biomarker of thrombosis associated with cancer. The objective was to compare the microparticulosome signature between patients presenting with thrombo-embolic event and those without. Methods: Patients with CRC and PC were prospectively included and divided in those with thrombo-embolic events (Group A) and those without (Group B).MPs were analyzed by flow cytometer, combining the analysis of Annexin V-positive with characterization of their origin and determination of their procoagulant activities. D-dimer levels were measured in the same samples. Results: We included 118 patients, divided in 19 patients with thrombo embolic event and 99 patients without. Fibrin-bearing MPs levels were significantly higher in presence of thrombo-embolic events, contrary to D-dimers levels. Fibrin-bearing MPs were more frequently produced by erythrocytes, endothelial cells or Ep-CAM+cells than platelets or leukocytes. Overall survival was shorter in case of thrombo-embolic events than without. The most frequent genes expressed by MPs derived from PC or CRC were implicated in metastatic diffusion of tumor cells, drug resistance, coagulation and inflammation. Conclusion: Circulating MPs, particularly fibrin-bearing MPs, could be used as a new biomarker to predict cancer-associated thrombo-embolic events and poor survival.

17.
Platelets ; : 1-7, 2017 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-29172822

RESUMO

Bivalirudin is associated with an increased risk of acute stent thrombosis (AST) compared to unfractionated heparin (UFH) in acute coronary syndrome patients (ACS) during short-duration percutaneous coronary intervention (PCI). The mechanisms involved are unknown. We aimed to investigate the antithrombotic efficacy of bivalirudin compared to UFH during PCI. In a monocenter study, we prospectively enrolled 30 patients undergoing PCI for a non-ST elevation ACS. They were randomly assigned to a single intravenous (IV) bolus of UFH (70 IU/kg) or an IV bolus of bivalirudin 0.75 mg/kg followed by a 1.75 mg/kg/h infusion during PCI. All patients received a loading dose (LD) of 180 mg of ticagrelor at the time of PCI. The VASP index and activated partial thromboplastin time (aPTT) were used to assess the course of platelet reactivity (PR) and antithrombotic activity. The two groups were similar regarding baseline, angiographic, and interventional characteristics. There was no difference between the two groups in the course of PR following ticagrelor LD. An optimal PR inhibition was obtained 4 h after the LD of ticagrelor. The level of antithrombotic activity was significantly lower in the bivalirudin group compared to the UFH group (p < 0.001) during PCI but similar at 2 and 4 h post-PCI. We observed that, in ACS undergoing PCI, the antithrombotic efficacy of an IV bolus of bivalirudin is significantly lower than that of a 70-IU/kg UFH bolus. This could contribute to the excess in thrombotic acute events observed during short-duration PCI.

18.
Sci Rep ; 7(1): 11801, 2017 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-28924220

RESUMO

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.

19.
Int J Cardiol ; 230: 427-431, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28041708

RESUMO

BACKGROUND: Altered coronary blood flow occurs in patients with coronary artery disease (CAD). Adenosine strongly impacts blood flow mostly via adenosine A2A receptor (A2AR) expressed in coronary tissues. As part of a systemic regulation of the adenosinergic system, we compared A2AR expression in situ, and on peripheral blood mononuclear cells (PBMC) in CAD patients. METHODS AND RESULTS: Aortic and coronary tissues, and PBMC were sampled in 20 CAD patients undergoing coronary artery bypass surgery and consecutively included. Controls were PBMC obtained from 15 healthy subjects. Expression and activity of A2AR were studied by Western blotting and cAMP measurement, respectively. A2AR expression on PBMC was lower in patients than in controls (0.83±0.31 vs 1.2±0.35 arbitrary units; p<0.01), and correlated with A2AR expression in coronary and aortic tissues (Pearson's r: 0.77 and 0.59, p<0.01, respectively). Basal and maximal cAMP productions following agonist stimulation of PBMC were significantly lower in patients than in controls (120±42 vs 191±65 and 360±113 vs 560±215pg/106 cells, p<0.05, respectively). In CAD patients, the increase from basal to maximal cAMP production in PBMC and aortic tissues was similar (+300% and +246%, respectively). CONCLUSION: Expression of A2AR on PBMC correlated with those measured in coronary artery and aortic tissues in CAD patients, A2AR activity of PBMC matched that observed in aorta, and A2AR expression and activity in PBMC were found reduced as compared to controls. Measuring the expression level of A2AR on PBMC represents a good tool to address in situ expression in coronary tissues of CAD patients.


Assuntos
Doença da Artéria Coronariana/metabolismo , Receptor A2A de Adenosina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta/metabolismo , Estudos de Casos e Controles , Ponte de Artéria Coronária , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/metabolismo , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade
20.
Heart Rhythm ; 14(2): 234-239, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27639455

RESUMO

BACKGROUND: "Unexplained syncope, no prodromes, and normal heart" has been described as a distinct clinical and biological entity. OBJECTIVE: The purpose of this study was to assess the mechanism of syncope. METHODS: In this prospective multicenter study, 58 patients presenting with unexplained syncope, no prodromes, and a normal heart received an implantable loop recorder (ILR) and were followed up until a diagnosis was established. Their outcomes were compared with those of 389 patients affected by reflex syncope with prodromes who received an ILR. RESULTS: During a mean observation period of 16 ± 13 months, a diagnostic event was documented by the ILR in 29 patients (50%); an asystolic pause of 11 ± 5 seconds (range 3.5-22 seconds) was present at the time of the diagnostic event in 19 patients (66%). Compared with patients affected by reflex syncope with prodromes, patients with unexplained syncope, no prodromes, and a normal heart more frequently had an asystolic syncope (66% vs 47%; P = .001), and this was more frequently due to idiopathic paroxysmal atrioventricular block (47% vs 21%; P = .04). Ten patients with asystolic pauses underwent cardiac pacing, and 8 patients underwent oral theophylline treatment. During the subsequent 17 ± 12 months of follow-up, syncope recurred in 1 patient on theophylline and presyncope occurred in 1 patient with pacemaker. CONCLUSION: A long asystolic pause, frequently due to idiopathic paroxysmal atrioventricular block, played a role in the mechanism of syncope in two-thirds of patients who had electrocardiographic documentation of a diagnostic event. When a specific therapy was administered in patients with asystolic syncope, the short outcome was favorable.


Assuntos
Bloqueio Atrioventricular , Estimulação Cardíaca Artificial , Parada Cardíaca , Síncope , Teofilina/administração & dosagem , Idoso , Bloqueio Atrioventricular/complicações , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/terapia , Estimulação Cardíaca Artificial/métodos , Eletrocardiografia Ambulatorial/métodos , Feminino , Parada Cardíaca/complicações , Parada Cardíaca/diagnóstico , Parada Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Síncope/diagnóstico , Síncope/etiologia , Síncope/fisiopatologia , Síncope/terapia , Resultado do Tratamento , Vasodilatadores/administração & dosagem
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