Publications by authors named "Régis Guieu"

114 Publications

Adenosine and neurohumoral syncope.

Minerva Med 2021 Apr 9. Epub 2021 Apr 9.

Laboratory of Biochemistry, Timone Hospital and C2VN INSERM, INRAE, Aix Marseille University, Marseille, France.

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 lowadenosine 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 two controlled studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0026-4806.21.07537-6DOI Listing
April 2021

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

Int J Mol Sci 2021 Feb 8;22(4). Epub 2021 Feb 8.

C2VN, INSERM, INRAE, Aix-Marseille University, F-13005 Marseille, France.

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 (HS) is a cardioprotector. Previous research proposed a positive role of HS in the cardiovascular system, and we discuss some recent data suggesting that HHCy worsens CVD by increasing the production of HS, which decreases the expression of adenosine A receptors on the surface of immune and cardiovascular cells to cause inflammation and ischemia, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22041690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914561PMC
February 2021

Hyperuricemia and Hypertension, Coronary Artery Disease, Kidney Disease: From Concept to Practice.

Int J Mol Sci 2020 Jun 6;21(11). Epub 2020 Jun 6.

Department of Cardiology, Aix-Marseille University, Hôpital Nord, 13015 Marseille, France.

Since the publication of the Framingham Heart Study, which suggested that uric acid should no longer be associated with coronary heart disease after additional adjustment for cardiovascular disease risk factors, the number of publications challenging this statement has dramatically increased. The aim of this paper was to review and discuss the most recent studies addressing the possible relation between sustained elevated serum uric acid levels and the onset or worsening of cardiovascular and renal diseases. Original studies involving American teenagers clearly showed that serum uric acid levels were directly correlated with systolic and diastolic pressures, which has been confirmed in adult cohorts revealing a 2.21-fold increased risk of hypertension. Several studies involving patients with coronary artery disease support a role for serum uric acid level as a marker and/or predictor for future cardiovascular mortality and long-term adverse events in patients with coronary artery disease. Retrospective analyses have shown an inverse relationship between serum uric acid levels and renal function, and even a mild hyperuricemia has been shown to be associated with chronic kidney disease in patients with type 2 diabetes. Interventional studies, although of small size, showed that uric acid (UA)-lowering therapies induced a reduction of blood pressure in teenagers and a protective effect on renal function. Taken together, these studies support a role for high serum uric acid levels (>6 mg/dL or 60 mg/L) in hypertension-associated morbidities and should bring awareness to physicians with regards to patients with chronic hyperuricemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21114066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312288PMC
June 2020

Elastase and exacerbation of neutrophil innate immunity are involved in multi-visceral manifestations of COVID-19.

Allergy 2021 Jan 23. Epub 2021 Jan 23.

Department Inserm UMRS_1116 DCAC, Université de Lorraine, Nancy, France.

Background: Many arguments suggest that neutrophils could play a prominent role in COVID-19. However, the role of key components of neutrophil innate immunity in severe forms of COVID-19 has deserved insufficient attention. We aimed to evaluate the involvement of neutrophil elastase, histone-DNA, and DNases in systemic and multi-organ manifestations of COVID-19.

Methods: We performed a multicenter study of markers of neutrophil innate immunity in 155 cases consecutively recruited in a screening center, local hospitals, and two regional university hospitals. The cases were evaluated according to clinical and biological markers of severity and multi-organ manifestations and compared to 35 healthy controls.

Results: Blood neutrophil elastase, histone-DNA, myeloperoxidase-DNA, and free dsDNA were dramatically increased, and DNase activity was decreased by 10-fold, compared with controls. Neutrophil elastase and histone-DNA were associated with intensive care admission, body temperature, lung damage, and markers of cardiovascular outcomes, renal failure, and increased interleukin-6 (IL-6), IL-8, and CXCR2. Neutrophil elastase was an independent predictor of the computed tomography score of COVID-19 lung damage and the number of affected organs, in multivariate analyses. The increased blood concentrations of NE and neutrophil extracellular traps were related to exacerbation of neutrophil stimulation through IL-8 and CXCR2 increased concentrations and increased serum DAMPs, and to impaired degradation of NETs as a consequence of the dramatic decrease in blood DNase activity.

Conclusion: Our results point out the key role of neutrophil innate immunity exacerbation in COVID-19. Neutrophil elastase and DNase could be potential biomarkers and therapeutic targets of severe systemic manifestations of COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014109PMC
January 2021

Correlation between low adenosine A receptor expression and hypercholesterolemia: A new component of the cardiovascular risk?

Biochim Biophys Acta Mol Cell Biol Lipids 2021 02 5;1866(2):158850. Epub 2020 Nov 5.

Aix-Marseille University, INSERM, INRAE, C2VN, Marseille, France; Laboratory of Biochemistry, Hôpital de La Timone, Marseille, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbalip.2020.158850DOI Listing
February 2021

Recent advances in the role of the adenosinergic system in coronary artery disease.

Cardiovasc Res 2021 Apr;117(5):1284-1294

C2VN, INSERM, INRAE, Aix-Marseille University, Campus Santé Timone, Faculté de Pharmacie, 27 Bd Jean Moulin, F-13005 Marseille, France.

Adenosine is an endogenous nucleoside that plays a major role in the physiology and physiopathology of the coronary artery system, mainly by activating its A2A receptors (A2AR). Adenosine is released by myocardial, endothelial, and immune cells during hypoxia, ischaemia, or inflammation, each condition being present in coronary artery disease (CAD). While activation of A2AR improves coronary blood circulation and leads to anti-inflammatory effects, down-regulation of A2AR has many deleterious effects during CAD. A decrease in the level and/or activity of A2AR leads to: (i) lack of vasodilation, which decreases blood flow, leading to a decrease in myocardial oxygenation and tissue hypoxia; (ii) an increase in the immune response, favouring inflammation; and (iii) platelet aggregation, which therefore participates, in part, in the formation of a fibrin-platelet thrombus after the rupture or erosion of the plaque, leading to the occurrence of acute coronary syndrome. Inflammation contributes to the development of atherosclerosis, leading to myocardial ischaemia, which in turn leads to tissue hypoxia. Therefore, a vicious circle is created that maintains and aggravates CAD. In some cases, studying the adenosinergic profile can help assess the severity of CAD. In fact, inducible ischaemia in CAD patients, as assessed by exercise stress test or fractional flow reserve, is associated with the presence of a reserve of A2AR called spare receptors. The purpose of this review is to present emerging experimental evidence supporting the existence of this adaptive adenosinergic response to ischaemia or inflammation in CAD. We believe that we have achieved a breakthrough in the understanding and modelling of spare A2AR, based upon a new concept allowing for a new and non-invasive CAD management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvaa275DOI Listing
April 2021

Blood myeloperoxidase-DNA, a biomarker of early response to SARS-CoV-2 infection?

Allergy 2021 03 17;76(3):892-896. Epub 2020 Aug 17.

Department INSERM, UMR_S1116 Défaillance cardiovasculaire aiguë et chronique, University of Lorraine, Nancy, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436665PMC
March 2021

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

Int J Mol Sci 2020 Jul 27;21(15). Epub 2020 Jul 27.

C2VN, INSERM, INRA, Aix-Marseille University, F-13015 Marseille, France.

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 AR, AR, AR, and AR. Among them, A subtypes are strongly expressed in coronary tissues, and their activation increases coronary blood flow via the production of cAMP in smooth muscle cells. A 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 A receptor subtypes. This review aims to focus on the specific exploration of the adenosine plasma level and its relationship with the A 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 A receptor agonists/antagonists are useful tools to improve the management of patients suffering from coronary artery disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21155321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432452PMC
July 2020

The prognostic value of serum procalcitonin in acute obstructive pyelonephritis.

World J Urol 2020 Jul 15. Epub 2020 Jul 15.

Department of Urology and Kidney Transplantation, Conception University Hospital, APHM, Aix-Marseille University, Marseille, France.

Purpose: To evaluate the prognostic value of procalcitonin (PCT) in the occurrence of infectious complications in the management of acute obstructive pyelonephritis (AOP) compared with other biological parameters (leucocyte count, C-reactive protein [CRP]).

Methods: We conducted a retrospective study including patients who were treated for AOP and performed serum PCT tests in our center between January 1, 2017 and December 31, 2017. Upper urinary tract obstruction was confirmed by either ultrasound or CT urography. Clinical examinations and laboratory tests including leukocyte count, CRP, urine and blood cultures, and serum PCT measurements were performed in the emergency unit. Treatment included early renal decompression using indwelling ureteral stents or nephrostomy and empiric antibiotic therapy. The primary endpoint was occurrence of severe sepsis (SS), a composite criterion including urosepsis and/or septic shock and/or admission to the intensive care unit (ICU) and/or death.

Results: A total of 110 patients (median age: 61 years) were included, of whom 56.3% were female. SS occurred in 39 cases (35.4%). Multivariate regression analysis showed that serum PCT (OR 1.08; 95% CI 1.03-1.17; p = 0.01), CRP (OR 1.007; 95% CI 1.001-1.015; p = 0.03), and diabetes mellitus (OR 5.1; 95% CI 1.27-27.24; p = 0.04) were independent predictors for SS. Serum PCT was the biological marker associated with the highest accuracy to predict SS (ROC 0.912 (95% CI 0.861-0.962) and was superior to CRP (p < 0.001): the sensitivity and specificity of PCT to predict SS were 95% and 77%, respectively, with a serum PCT cutoff value of 1.12 µg/L.

Conclusions: PCT levels > 1.12 µg/L could help physicians to identify high-risk patients who could benefit from early and aggressive management in collaboration with intensive care specialists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00345-020-03353-2DOI Listing
July 2020

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

J Cell Mol Med 2020 08 29;24(16):8942-8949. Epub 2020 Jun 29.

C2VN, INSERM, INRA, Aix Marseille University, Marseille, France.

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 A receptors (A R). We addressed in CAD patients the relationship between HCy and A R production, and in cellulo the effect of HCy on A R function. 46 patients with CAD and 20 control healthy subjects were included. We evaluated A R production by peripheral blood mononuclear cells using Western blotting. We studied in cellulo (CEM human T cells) the effect of HCy on A R production as well as on basal and stimulated cAMP production following A 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). A 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 A R production (r = -0.43; P < 0.0001), with decreased A R production above 25 µM HCy. In cellulo, HCy inhibited A R production, as well as basal and stimulated cAMP production. In conclusion, HCy is negatively associated with A R production in CAD patients, as well as with A R and cAMP production in cellulo. The decrease in A R production and function, which is known to hamper coronary blood flow and promote inflammation, may support CAD pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.15527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417719PMC
August 2020

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

Europace 2020 06;22(6):847-853

Laboratory of Biochemistry, Timone Hospital, Marseille, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/europace/euaa070DOI Listing
June 2020

Adenosine and the Cardiovascular System: The Good and the Bad.

J Clin Med 2020 May 6;9(5). Epub 2020 May 6.

Department of Medicine and Surgery, University of Milano Bicocca, 20122 Milan, Italy.

Adenosine is a nucleoside that impacts the cardiovascular system via the activation of its membrane receptors, named AR, AR, AR and AR. Adenosine is released during hypoxia, ischemia, beta-adrenergic stimulation or inflammation and impacts heart rhythm and produces strong vasodilation in the systemic, coronary or pulmonary vascular system. This review summarizes the main role of adenosine on the cardiovascular system in several diseases and conditions. Adenosine release participates directly in the pathophysiology of atrial fibrillation and neurohumoral syncope. Adenosine has a key role in the adaptive response in pulmonary hypertension and heart failure, with the most relevant effects being slowing of heart rhythm, coronary vasodilation and decreasing blood pressure. In other conditions, such as altitude or apnea-induced hypoxia, obstructive sleep apnea, or systemic hypertension, the adenosinergic system activation appears in a context of an adaptive response. Due to its short half-life, adenosine allows very rapid adaptation of the cardiovascular system. Finally, the effects of adenosine on the cardiovascular system are sometimes beneficial and other times harmful. Future research should aim to develop modulating agents of adenosine receptors to slow down or conversely amplify the adenosinergic response according to the occurrence of different pathologic conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9051366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290927PMC
May 2020

Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome.

J Transl Med 2020 04 19;18(1):173. Epub 2020 Apr 19.

Department of Internal Medicine, European Hospital, Marseille, France.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12967-020-02341-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168976PMC
April 2020

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

Front Physiol 2020 11;11:97. Epub 2020 Feb 11.

Laboratoire Impact de l'Activité Physique sur la Santé, UFR STAPS, Université de Toulon, La Garde, France.

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, < 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 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, respectively < 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2020.00097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026462PMC
February 2020

Adenosine Receptor Profiling Reveals an Association between the Presence of Spare Receptors and Cardiovascular Disorders.

Int J Mol Sci 2019 Nov 27;20(23). Epub 2019 Nov 27.

C2VN, INSERM, INRA, Aix-Marseille University, F-13015 Marseille, France.

Adenosine and its receptors exert a potent control on the cardiovascular system. This review aims to present emerging experimental evidence supporting the existence and implication in cardiovascular disorders of specific adenosinergic pharmacological profiles, conforming to the concept of "receptor reserve", also known as "spare receptors". This kind of receptors allow agonists to achieve their maximal effect without occupying all of the relevant cell receptors. In the cardiovascular system, spare adenosine receptors appear to compensate for a low extracellular adenosine level and/or a low adenosine receptor number, such as in coronary artery disease or some kinds of neurocardiogenic syncopes. In both cases, the presence of spare receptors appears to be an attempt to overcome a weak interaction between adenosine and its receptors. The identification of adenosine spare receptors in cardiovascular disorders may be helpful for diagnostic purposes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20235964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928742PMC
November 2019

Extracellular vesicles with ubiquitinated adenosine A receptor in plasma of patients with coronary artery disease.

J Cell Mol Med 2019 10 24;23(10):6805-6811. Epub 2019 Aug 24.

Center for CardioVascular and Nutrition Research (C2VN), INSERM, INRA and Aix-Marseille University, Marseille, France.

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 A receptor (A 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 A R. Interestingly, the presence of ubiquitinated A R in EV from patients was dependent on hyperhomocysteinemia, the amount being inversely proportional to A 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 A R in stimulated conditions depending on the hypoxic status and HCy level of culture medium. Together, these data show that ubiquitinated A R-containing EV circulate in the plasma of CAD patients and that this presence is related to hyperhomocysteinemia. A R in plasma EV could be a useful tool for diagnosis and a promising drug for the treatment of CAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.14564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787504PMC
October 2019

Efficacy of theophylline in patients with syncope without prodromes with normal heart and normal ECG.

Int J Cardiol 2019 08 22;289:70-73. Epub 2019 Mar 22.

Department of Cardiology, Hopital La Timone Adultes, Marseille, France; UMR MD2, Aix Marseille University, Institute of Biological research of the French Army (IRBA), Marseille, France.

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 ± 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2019.03.043DOI Listing
August 2019

Sudden Onset Nephrotic-Range Proteinuria.

Clin Chem 2019 04;65(4):600-601

Service de Biochimie, Timone University Hospital, AP-HM, Marseille, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1373/clinchem.2018.295519DOI Listing
April 2019

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

Physiol Rep 2019 03;7(6):e14033

C2VN, INSERM, INRA, Aix-Marseille Université (AMU), Marseille, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14814/phy2.14033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434169PMC
March 2019

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

Int J Cardiol 2019 06 27;285:121-127. Epub 2019 Feb 27.

Center for CardioVascular and Nutrition Research (C2VN), INSERM, INRA and Aix-Marseille University, Marseille, France.

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 A receptor (AR). We evaluated AR 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 AR was studied, using a AR monoclonal antibody with agonist properties, allowing determination of AR affinity (K) and cAMP production (ie.EC).

Results: AR 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 AR 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/10 cells (P < 0.05) and 375 [160-659] vs 670 [410-980] pg/10 cells (P < 0.05), respectively. A high K/EC ratio, characteristic of spare receptors, was observed in CAD with inducible-myocardial-ischemia.

Conclusion: AR expression in the arteries of patients, correlated with their expression in PBMCs. AR expression was lower in patients than in controls. A single blood sample (for measurement of AR 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2019.02.055DOI Listing
June 2019

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

Purinergic Signal 2019 03 7;15(1):45-52. Epub 2018 Dec 7.

Department of Cardiology, Timone University Hospital, 13005, Marseille, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11302-018-9636-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439011PMC
March 2019

Troponins in scuba divers with immersion pulmonary edema.

Biosci Rep 2018 10 28;38(5). Epub 2018 Sep 28.

Diving and Hyperbaric Center, Geneva University Hospital, Centre for Cardiovascular Disease and Nutrition, Bvd J Moulin, Marseille 13005, France.

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 (<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, (=0.008) and 128 ± 42 compared with 269 ± 210, (=0.01), respectively; no significant change was observed concerning TnI-us (pg/ml): 110 ± 34 compared with 330 ± 77, =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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/BSR20181024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165839PMC
October 2018

Adenosine Plasma Level and A2A Receptor Expression in Patients With Cardiogenic Shock.

Crit Care Med 2018 09;46(9):e874-e880

Department of Cardiology, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000003252DOI Listing
September 2018

Adenosine hypersensitivity and atrioventricular block.

Herzschrittmacherther Elektrophysiol 2018 Jun 29;29(2):166-170. Epub 2018 May 29.

Service de Cardiologie, CHU La Timone, 13005, Marseille, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00399-018-0570-2DOI Listing
June 2018

Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: A randomised controlled clinical trial.

Eur J Anaesthesiol 2018 12;35(12):911-918

From the Department of Anaesthesia and Intensive Care Medicine (DL, LN, FK, NB, LV, CG), Department of Biochemistry (RG, EF), Department of Biostatistics (NR, RG), Department of Cardiac Surgery (AT, DG, VG), La Timone University Hospital, Aix-Marseille University, Marseille, France (FC).

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/EJA.0000000000000824DOI Listing
December 2018

Specific Pharmacological Profile of A Adenosine Receptor Predicts Reduced Fractional Flow Reserve in Patients With Suspected Coronary Artery Disease.

J Am Heart Assoc 2018 04 13;7(8). Epub 2018 Apr 13.

UMR MD2, Aix-Marseille University, Marseille, France.

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 A receptors (AR)-characterized by a high dissociation constant/half maximal effective concentration (K/EC) 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 AR 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 (K), functional response (cyclic adenosine monophosphate [cAMP] production; EC) on PBMC 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 K/EC 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 AR on PBMC may help to rule out myocardial ischemia.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03218007.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.117.008290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015402PMC
April 2018

Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome.

Purinergic Signal 2018 06 6;14(2):191-199. Epub 2018 Apr 6.

Department of Cardiology, Hopital Nord, Marseille, France.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11302-018-9604-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940631PMC
June 2018

Corrigendum to "A case of false positive cardiac troponin I in CANOMAD syndrome" [Int. J. Cardiol. 222 (2016) 359-360].

Int J Cardiol 2018 05 27;259:234. Epub 2018 Feb 27.

Laboratory of Biochemistry, Timone University Hospital, France; UMR MD2, Aix Marseille University (AMU), France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2018.02.017DOI Listing
May 2018

BotAF, a new Buthus occitanus tunetanus scorpion toxin, produces potent analgesia in rodents.

Toxicon 2018 Jul 12;149:72-85. Epub 2018 Jan 12.

Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire des Venins et Biomolécules Thérapeutiques, 13, Place Pasteur BP-74, Tunis, 1002, Tunisia. Electronic address:

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 β-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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxicon.2018.01.003DOI Listing
July 2018