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This study aimed to assess the utility of echocardiography-measured epicardial adipose tissue (EAT) thickness (EATT) as an independent predictor for coronary artery disease (CAD), examining its correlation with oxidative stress levels in epicardial tissue and the complexity of the disease in patients undergoing open-heart surgery. This study included a total of 25 patients referred for cardiac surgery with 14 in the CAD group and 11 in the non-CAD group. Epicardial fat was sampled from patients subjected to open-heart surgery. EATT was higher in the CAD group compared to the non-CAD group (8.15 ± 2.09 mm vs. 5.12 ± 1.8 mm, p = 0.001). The epicardial reactive oxygen species level was higher in the CAD group compared to the non-CAD group (21.4 ± 2.47 nmol H2O2/g tisssue/h vs. 15.7 ± 1.55 nmol H2O2/g tisssue/h, p < 0.001). EATT greater than 6.05 mm was associated with CAD, with a sensitivity of 86% and specificity of 73%. Echocardiographically measured EATT is a significant, independent predictor of CAD. Its relationship with increased EAT oxidative stress levels suggests a potential mechanistic link between EATT and CAD pathogenesis. These findings highlight the importance of EATT as a diagnostic tool in assessing the complexity of CAD in patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Monoamine oxidases (MAOs), mitochondrial enzymes that constantly produce hydrogen peroxide (H2O2) as a byproduct of their activity, have been recently acknowledged as contributors to oxidative stress in cardiometabolic pathologies. The present study aimed to assess whether MAOs are mediators of valvular oxidative stress and interact in vitro with angiotensin 2 (ANG2) to mimic the activation of the renin–angiotensin system. To this aim, valvular tissue samples were harvested from 30 patients diagnosed with severe primary mitral regurgitation and indication for surgical repair. Their reactive oxygen species (ROS) levels were assessed by means of a ferrous oxidation xylenol orange (FOX) assay, while MAO expression was assessed by immune fluorescence (protein) and qRT-PCR (mRNA). The experiments were performed using native valvular tissue acutely incubated or not with angiotensin 2 (ANG2), MAO inhibitors (MAOI) and the angiotensin receptor blocker, irbesartan (Irb). Correlations between oxidative stress and echocardiographic parameters were also analyzed. Ex vivo incubation with ANG2 increased MAO-A and -B expression and ROS generation. The level of valvular oxidative stress was negatively correlated with the left ventricular ejection fraction. MAOI and Irb reduced valvular H2O2. production. In conclusion, both MAO isoforms are expressed in pathological human mitral valves and contribute to local oxidative stress and ventricular functional impairment and can be modulated by the local renin–angiotensin system. [ABSTRACT FROM AUTHOR]

Sodium–glucose cotransporter 2 inhibitors (SGLT2i), a novel class of glucose-lowering drugs, have revolutionized the management of heart failure with reduced and preserved ejection fraction, regardless of the presence of diabetes, and are currently incorporated in the heart failure guidelines. While these drugs have consistently demonstrated their ability to decrease heart failure hospitalizations in several landmark clinical trials, their cardioprotective effects are far from having been completely elucidated. In the past decade, a growing body of experimental research has sought to address the molecular and cellular mechanisms of SGLT2i in order to provide a better understanding of the off-target acute and chronic cardiac benefits, beyond the on-target renal effect responsible for blood glucose reduction. The present narrative review addresses the direct cardioprotective effects of SGLT2i, delving into the off-target mechanisms of the drugs currently approved for heart failure therapy, and provides insights into future perspectives. [ABSTRACT FROM AUTHOR]

In recent years, the worldwide epidemic of metabolic diseases, namely obesity, metabolic syndrome, diabetes and metabolic-associated fatty liver disease (MAFLD) has been strongly associated with constant exposure to endocrine-disruptive chemicals (EDCs), in particular, the ones able to disrupt various metabolic pathways. EDCs have a negative impact on several human tissues/systems, including metabolically active organs, such as the liver and pancreas. Among their deleterious effects, EDCs induce mitochondrial dysfunction and oxidative stress, which are also the major pathophysiological mechanisms underlying metabolic diseases. In this narrative review, we delve into the current literature on EDC toxicity effects on the liver and pancreatic tissues in terms of impaired mitochondrial function and redox homeostasis. [ABSTRACT FROM AUTHOR]

Introduction Obesity is an age-independent, lifestyle-triggered, rapidly expanding pandemic disease (Bhupathiraju and Hu 2016) characterized by chronic systemic and adipose tissue inflammation as the major pathomechanism (Goran and Alderete 2012; [...], Obesity is an age-independent, lifestyle-triggered, pandemic disease associated with both endothelial and visceral adipose tissue (VAT) dysfunction leading to cardiometabolic complications mediated via increased oxidative stress and persistent chronic inflammation. The purpose of the present study was to assess the oxidative stress in VAT and vascular samples and the effect of in vitro administration of vitamin D. VAT and mesenteric artery branches were harvested during abdominal surgery performed on patients referred for general surgery (n = 30) that were randomized into two subgroups: nonobese and obese. Serum levels of C-reactive protein (CRP) and vitamin D were measured. Tissue samples were treated or not with the active form of vitamin D: 1,25[(OH).sub.2][D.sub.3] (100 nmol/L, 12 h). The main findings are that in obese patients, (i) a low vitamin D status was associated with increased inflammatory markers and reactive oxygen species generation in VAT and vascular samples and (ii) in vitro incubation with vitamin D alleviated oxidative stress in VAT and vascular preparations and also improved the vascular function. We report here that the serum level of vitamin D is inversely correlated with the magnitude of oxidative stress in the adipose tissue. Ex vivo treatment with active vitamin D mitigated obesity-related oxidative stress. Key words: visceral adipose tissue, mesenteric arteries, oxidative stress, endothelial dysfunction. Resume : L'obesite est une maladie pandemique, independante de l'age et declenchee par le mode de vie qui est associee a des dysfonctionnements endotheliaux comme du tissu adipeux visceral (TAV) et qui mene a des complications cardiometaboliques mediees par l'intermediaire d'une augmentation du stress oxydatif et de la persistance d'une inflammation chronique. La presente etude visait a evaluer le stress oxydatif dans des echantillons de TAV et de vaisseaux, ainsi que l'effet de l'administration de vitamine D in vitro. Nous avons preleve du TAV et des rameaux d'artere mesenterique au cours d'interventions chirurgicales abdominales effectuees chez des patients diriges en chirurgie generale (n = 30), que nous avons repartis aleatoirement dans deux sous-groupes : non-obeses et obeses. Nous avons mesure les taux seriques de proteine C reactive et de vitamine D. Nous avons mis des echantillons de tissu en presence ou non de la forme active de la vitamine D--1,25[(OH).sub.2][D.sub.3] (100 nM, 12 h). Voici nos principaux resultats chez les patients obeses : (i) association de faibles taux de vitamine D avec une hausse des marqueurs de l'inflammation et de la production de derives reactifs de l'oxygene dans les echantillons de TAV et de vaisseaux et (ii) l'incubation avec de la vitamine D in vitro permettait d'attenuer le stress oxydatif dans les preparations de TAV et de vaisseaux, avec aussi une amelioration sur le plan du fonctionnement des vaisseaux. Nous rapportons ici que les taux seriques de vitamine D sont inversement proportionnels a l'ampleur du stress oxydatif dans le tissu adipeux. L'administration ex vivo de vitamine D active permettait d'attenuer le stress oxydatif lie a l'obesite. [Traduit par la Redaction] Mots-cles : tissu adipeux visceral, arteres mesenteriques, stress oxydatif, dysfonctionnement endothelial.

Introduction Obesity is the most important modifiable risk factor for morbidity and mortality due to life-threatening cardiovascular diseases, type 2 diabetes, and certain cancers. With the increased adoption of the [...], Obesity is an important preventable risk factor for morbidity and mortality from cardiometabolic disease. Oxidative stress (including in visceral adipose tissue) and chronic low-grade inflammation are the major underlying pathomechanisms. Monoamine oxidase (MAO) has recently emerged as an important source of cardiovascular oxidative stress. The present study was conducted to evaluate the role of MAO as contributor to reactive oxygen species (ROS) production in white adipose tissue and vessels harvested from patients undergoing elective abdominal surgery. To this aim, visceral adipose tissue and mesenteric artery branches were isolated from obese patients with chronic inflammation and used for organ bath, ROS production, quantitative real-time PCR, and immunohistology studies. The human visceral adipose tissue and mesenteric artery branches contain mainly the MAO-A isoform, as shown by the quantitative real-time PCR and immunohistology experiments. A significant upregulation of MAO-A, the impairment in vascular reactivity, and increase in ROS production were found in obese vs. non-obese patients. Incubation of the adipose tissue samples and vascular rings with the MAO-A inhibitor (clorgyline, 30 min) improved vascular reactivity and decreased ROS generation. In conclusion, MAO-A is the predominant isoform in human abdominal adipose and vascular tissues, is overexpressed in the setting of inflammation, and contributes to the endothelial dysfunction. Key words: monoamine oxidases, obesity, inflammation, endothelial dysfunction. L&apos;obesite est un important facteur de risque de morbidite et de mortalite liees a la maladie cardiometabolique qu&apos;il est possible de prevenir. Le stress oxydatif (y compris dans le tissu adipeux visceral) et l&apos;inflammation chronique de faible intensite en sont les principaux modes d&apos;action sous-jacents. La monoamine-oxydase (MAO) est depuis peu reconnue comme etant une importante source de stress oxydatif cardiovasculaire. La presente etude a ete menee en vue d&apos;evaluer la contribution de la MAO pour la production de derives reactifs de l&apos;oxygene dans du tissu adipeux blanc et des vaisseaux sanguins preleves chez des patients subissant une intervention chirurgicale abdominale elective. A cette fin, nous avons isole du tissu adipeux visceral et des rameaux d&apos;artere mesenterique chez des patients obeses presentant une inflammation chronique en vue de proceder a des etudes (i) en bain de tissu, (ii) sur la production de derives reactifs de l&apos;oxygene, (iii) de PCR quantitatif en temps reel et (iv) d&apos;immunohistologie. Comme l&apos;ont montre ces deux dernieres techniques, chez l&apos;homme, le tissu adipeux visceral et les rameaux d&apos;artere mesenterique contiennent principalement l&apos;isoforme MAO-A. Nous avons observe une regulation a la hausse de la MAO-A, une diminution de la reactivite vasculaire et une augmentation de la production de derives reactifs de l&apos;oxygene plus marquer chez les patients obeses que chez les patients non obeses. L&apos;incubation des echantillons de tissu adipeux et des anneaux vasculaires avec de la clorgyline (un inhibiteur de la MAO-A) pendant 30 minutes a permis d&apos;ameliorer la reactivite vasculaire et de faire diminuer la production de derives reactifs de l&apos;oxygene. En conclusion, la MAO-A est l&apos;isoforme predominante dans les tissus adipeux et vasculaire abdominaux humains, est surexprimee en contexte d&apos;inflammation et participe au dysfonctionnement endothelial. [Traduit par la Redaction] Mots-cles: monoamine-oxydases, obesite, inflammation, dysfonctionnement endothelial.

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-β-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)—the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Introduction Diabetes mellitus (DM), a well-established independent risk factor for coronary heart disease, is currently the most serious threat to humanity health worldwide due to its alarming increase in prevalence [...], Endothelial dysfunction and the related increase in reactive oxygen species (ROS) production are important events in the pathophysiology of diabetes mellitus (DM). Methylene blue (MB) has been systematically investigated for its protective effects against refractory hypotension and mitochondrial dysfunction. We have previously demonstrated that MB improved mitochondrial respiration and partially decreased oxidative stress in diabetic rat hearts. The present study was aimed to investigate whether MB modulates vascular function and ROS production in thoracic aortic rings isolated from rats with streptozotocin-induced DM (after 4 weeks of hyperglycemia). The effects of MB (0.1 [micro]M, 30 min ex vivo incubation) on vascular reactivity in organ chamber (phenylephrine-induced contraction, acetylcholine-induced relaxation) and [H.sub.2][O.sub.2] production (assessed by ferrous iron xylenol orange oxidation assay) were investigated in vascular preparations with intact endothelium and after denudation. DM elicited a significant alteration of vascular function: increased contractility to phenylephrine, attenuation of acetylcholinedependent relaxation, and augmented [H.sub.2][O.sub.2] generation. Ex vivo incubation with MB partially reversed all these changes (by approximately 70%) in vascular segments with intact endothelial layer (but not in denuded vessels). In conclusion, MB might be useful in alleviating endothelial dysfunction and mitigating endothelial oxidative stress, observations that clearly require further investigation in the setting of cardiometabolic disease. Key words: methylene blue, endothelial dysfunction, oxidative stress, experimental diabetes. Le dysfonctionnement endothelial et l&apos;augmentation de la production de derives reactifs de l&apos;oxygene (ou ROS pour <>) qui y est liee constituent des evenements importants dans la physiopathologie du diabete sucre (DS). Le bleu de methylene (BM) a ete etudie systematiquement pour ses effets protecteurs contre l&apos;hypotension refractaire et le dysfonctionnement mitochondrial. Nous avons montre precedemment que le BM permet d&apos;ameliorer la respiration mitochondriale ainsi que de faire diminuer partiellement le stress oxydatif dans le creur du rat atteint de DS. Les presents travaux visaient a etudier si le BM permet de moduler la fonction vasculaire et la production de ROS dans des anneaux d&apos;aortes thoraciques isolees de rats atteints de DS provoque par la streptozotocine (apres 4 semaines d&apos;hyperglycemie). Nous avons etudie les effets du BM (a 0,1 [micro]M, incubation ex vivo de 30 minutes) sur la reactivite vasculaire en chambre d&apos;organes (contraction provoquee par la phenylephrine, relaxation provoquee par l&apos;acetylcholine) et la production de [H.sub.2][O.sub.2] (evaluee a l&apos;aide du test d&apos;oxydation de fer ferreux en presence de xylenol orange) dans des preparations vasculaires dont l&apos;endothelium etait intact et apres denudation. Le DS a entraine une degradation notable de la fonction vasculaire : augmentation de la contractilite en reaction a la phenylephrine, attenuation de la relaxation dependante de l&apos;acetylcholine et augmentation de la production d&apos;[H.sub.2][O.sub.2]. L&apos;incubation ex vivo avec du BM a permis d&apos;inverser partiellement toutes ces variations (d&apos;environ 70 %) dans les segments vasculaires dotes d&apos;une couche endotheliale intacte (mais pas dans les vaisseaux denudes). En conclusion, le BM pourrait etre utile en vue d&apos;attenuer le dysfonctionnement endothelial et le stress oxydatif endothelial. Ce sont des observations qui demanderaient clairement des recherches plus poussees dans un contexte de maladie cardiometabolique. [Traduit par la Redaction] Mots-cles: bleu de methylene, dysfonctionnement endothelial, stress oxydatif, diabete experimental.

Introduction Coronary heart disease is the leading cause of mortality due to myocardial infarction and of morbidity due to heart failure. In the past decades, mitochondrial dysfunction has emerged as [...], Diabetic cardiomyopathy has been systematically associated with compromised mitochondrial energetics and increased generation of reactive oxygen species (ROS) that underlie its progression to heart failure. Methylene blue is a redox drug with reported protective effects mainly on brain mitochondria. The purpose of the present study was to characterize the effects of acute administration of methylene blue on mitochondrial respiration, [H.sub.2][O.sub.2] production, and calcium sensitivity in rat heart mitochondria isolated from healthy and 2 months (streptozotocin-induced) diabetic rats. Mitochondrial respiratory function was assessed by high-resolution respirometry. [H.sub.2][O.sub.2] production and calcium retention capacity were measured spectrofluorimetrically. The addition of methylene blue (0.1 [micro]mol x [L.sup.-1]) elicited an increase in oxygen consumption of mitochondria energized with complex I and II substrates in both normal and diseased mitochondria. Interestingly, methylene blue elicited a significant increase in [H.sub.2][O.sub.2] release in the presence of complex I substrates (glutamate and malate), but had an opposite effect in mitochondria energized with complex II substrate (succinate). No changes in the calcium retention capacity of healthy or diabetic mitochondria were found in the presence of methylene blue. In conclusion, in cardiac mitochondria isolated from diabetic and nondiabetic rat hearts, methylene blue improved respiratory function and elicited a dichotomic, substrate-dependent effect on ROS production. Key words: rat heart mitochondria, diabetes mellitus, methylene blue, mitochondrial respiration, reactive oxygen species. On a systematiquement associe la cardiomyopathie diabetique a une atteinte de la fonction energetique des mitochondries et a une augmentation de la production de derives reactifs de l&apos;oxygene (ROS), lesquels phenomenes sous-tendent son evolution vers l&apos;insuffisance cardiaque. Le bleu de methylene est un medicament redox avec des effets protecteurs rapportes principalement dans les mitochondries cerebrales. La presente etude a ete realisee en vue de caracteriser les effets de l&apos;administration aigue de bleu de methylene sur la respiration mitochondriale, la production de [H.sub.2][O.sub.2] et la sensibilite au calcium dans des mitochondries isolees de creurs de rats sains ou diabetiques de 2 mois (diabete provoque par la streptozotocine). Nous avons evalue la fonction respiratoire mitochondriale a l&apos;aide de la respirometrie a haute resolution. Nous avons mesure la production de peroxyde d&apos;hydrogene et la capacite de retention calcique a l&apos;aide de la spectrofluorometrie. L&apos;ajout de bleu de methylene (0,1 [micro]mol x [L.sup.-1]) a provoque une augmentation de la consommation d&apos;oxygene par des mitochondries energisees par des substrats des complexes I et II, et ce, chez les mitochondries normales et lesees a la fois. Il est interessant de noter que le bleu de methylene a provoque une augmentation marquee de la liberation de [H.sub.2][O.sub.2] en presence de substrats du complexe I (glutamate et malate), mais qu&apos;il avait un effet contraire dans les mitochondries energisees avec le substrat du complexe II (succinate). En presence de bleu de methylene, nous n&apos;avons observe aucune variation de la capacite de retention du calcium dans les mitochondries saines ou diabetiques. En conclusion, dans les mitochondries isolees de creurs de rats sains ou diabetiques, le bleu de methylene permettait d&apos;ameliorer la fonction respiratoire et provoquait un effet dichotomique et dependant du substrat sur la production de ROS. [Traduit par la Redaction] Mots-cles : mitochondrie de creur de rat, diabete sucre, bleu de methylene, respiration mitochondriale, derives reactifs de l&apos;oxygene.

Introduction Chronic kidney disease (CKD) is a characterized by an irreversible alteration of renal structure and function, lasting more than 3 months, and the association with a plethora of complications: [...], Arteriovenous fistula (AVF) is the "lifeline" for patients with end-stage renal disease (ESRD) undergoing hemodialysis. AVF maturation failure is a poorly understood process, one of the contributors being endothelial dysfunction due to oxidative stress. Monoamine oxidases (MAOs) A and B were recently identified as novel sources of vascular oxidative stress. The aim of the present study was to assess the contribution of MAOs to the endothelial dysfunction in patients with ESDR with indication of hemodialysis. Fragments of brachial artery collaterals were harvested from ESRD patients during the surgical procedure aimed at creating the vascular access in the cubital fossa. The effect of increasing concentrations (10, 30,100 [micro]mol/L) of the irreversible MAO-A inhibitor, clorgyline, and MAO-B inhibitor, selegiline, on endothelial-dependent relaxation (EDR) in response to cumulative doses of acetylcholine was studied in isolated phenylephrine-preconstricted vascular rings. Hydrogen peroxide ([H.sub.2][O.sub.2]) production was assessed using ferrous oxidation xylenol orange assay. We showed that incubation of brachial rings with MAO inhibitors significantly improved EDR and attenuated [H.sub.2][O.sub.2] generation in patients with ESRD. MAO-related oxidative stress might contribute to the primary dysfunction/non-maturation of the AVF and MAO inhibitors could improve maturation and long-term patency of the vascular access in dialysis patients. Key words: arteriovenous fistula, monoamine oxidases, oxidative stress, endothelial dysfunction. La fistule arterioveineuse (FAV) represente la ligne de vie des patients atteints d&apos;insuffisance renale terminale (IRT) hemodialyses. L&apos;echec de la maturation de la FAV est un processus que l&apos;on comprend mal, l&apos;un des facteurs contributeurs etant le dysfonctionnement endothelial cause par le stress oxydatif. On a recemment caracterise les monoamines-oxydases (MAO) A et B comme etant de nouvelles sources de stress oxydatif vasculaire. La presente etude avait comme objectif d&apos;evaluer la contribution des MAO dans le dysfonction endothelial chez des patients atteints d&apos;IRT avec indication d&apos;hemodialyse. Nous avons preleve des fragments de collaterales d&apos;arteres brachiales de patients atteints d&apos;IRT pendant l&apos;intervention chirurgicale visant a creer l&apos;acces vasculaire dans le pli du coude. Nous avons etudie l&apos;effet de concentrations croissantes (10, 30,100 [micro]mol/L) de clorgyline, un inhibiteur irreversible de la MAO-A, et de selegiline, un inhibiteur de la MAO-B, sur la relaxation dependante de l&apos;endothelium (RDE) en reaction a des doses cumulatives d&apos;acetylcholine dans des anneaux vasculaires isoles precontractes par la phenylephrine. Nous avons evalue la production de peroxyde d&apos;hydrogene ([H.sub.2][O.sub.2]) a l&apos;aide de l&apos;epreuve d&apos;oxydation ferreuse avec l&apos;orange de xylenol. Nous avons montre que l&apos;incubation d&apos;anneaux brachiaux avec des inhibiteurs de la MAO permettait nettement d&apos;ameliorer la RDE et d&apos;attenuer la production d&apos;[H.sub.2][O.sub.2] chez les patients atteints d&apos;IRT. Le stress oxydatif lie aux MAO pourrait contribuer au dysfonctionnement ou a la non-maturation primaires de la FAV, et les inhibiteurs de la MAO pourraient permettre d&apos;ameliorer la maturation et la permeabilite a long terme de l&apos;acces vasculaire chez les patients dialyses. [Traduit par la Redaction] Mots-cles: fistule arterioveineuse, monoamines-oxydases, stress oxydatif, dysfonctionnement endothelial.

Introduction Cardiac imaging is indispensable for managing the care of heart failure (HF) patients. Prognosis in cardiac disease is closely related to systolic function, which is commonly assessed using left [...], In previous studies, mechanical dispersion (MD) predicted ventricular arrhythmias independently of left ventricular ejection fraction (LVEF). Moreover, the combination of MD and global longitudinal strain (GLS) increased the prediction of arrhythmic events. We investigated the prognostic value of a new 2-dimensional strain index, GLS/MD, in patients with heart failure (HF). We analyzed 340 consecutive HF outpatients in sinus rhythm. Echocardiography was performed at 1.6 [+ or -] 0.4 months after hospital discharge. The end point included sudden cardiac death, ventricular fibrillation, and sustained ventricular tachycardia (SCD/VA). During the follow-up period (36 [+ or -] 9 months), SCD/VA occurred in 48 patients (14.1%). A multivariate Cox regression analysis, which included LVEF, early diastolic transmitral / mitral annular velocity ratio (E/E&apos;), GLS, MD, and GLS/MD in the model, revealed that GLS/MD was the best independent predictor of SCD/VA (HR = 3.22, 95% confidence interval = 1.72-6.15, p = 0.03). Separate inclusion of LVEF, systolic mitral annular velocity, E/E&apos;, GLS, and MD together with GLS/MD showed that GLS/MD remained the best predictor of SCD/VA (each p Key words: heart failure, malignant ventricular arrhythmia, cardiovascular risk stratification, 2D strain imaging, global longitudinal strain, mechanical dispersion, GLS/MD ratio. Dans des etudes anterieures, la dispersion mecanique (DM) etait un facteur predictif des arythmies ventriculaires independant de la fraction d&apos;ejection ventriculaire gauche (FEVG). De plus, l&apos;association de la DM avec le strain longitudinal global (SLG) augmentait la predictibilite des evenements arythmiques. Nous avons etudie la valeur pronostique du ratio SLG/DM, un nouvel indice de strain bidimensionnel, chez des patients atteints d&apos;insuffisance cardiaque (IC). Nous avons etudie en consultations externes 340 patients atteints d&apos;IC consecutifs, qui affichaient un rythme sinusal. Nous avons effectue une echocardiographie 1,6 [+ or -] 0,4 mois apres le conge de l&apos;hopital. Le parametre devaluation (MSC/AV) etait compose des elements suivants : mort subite cardiaque, fibrillation ventriculaire ou tachycardie ventriculaire soutenue. Pendant la periode de suivi (36 [+ or -] 9 mois) le MSC/AVest survenu chez 48 patients (14,1 %). Al&apos;aide d&apos;une analyse de regression multivariee de Cox comprenant dans le modele la FEVG, le rapport des vitesses diastoliques precoces transmitrale/anneau mitral (E/E&apos;), le SLG, la DM et le ratio SLG/DM, le ratio SLG/DM etait le meilleur facteur predictif independant pour le SCD/VA (rapport de risques instantanes (RRI) de 3,22 avec un intervalle de confiance a 95 % de 1,72 a 6,15, p = 0,03). L&apos;inclusion de la FEVG, de la vitesse annulaire transmitrale systolique, du rapport E/E&apos;, du SLG et de la DM separement avec le ratio SLG/DM a montre que le ratio SLG/DM demeure le meilleur facteur predictif de MSC/AV (chacun p < 0,05). La valeur predictive limite optimale du ratio SLG/DM pour le MSC/AV etait de -0,20 %/ms (sensibilite de 80 %, specificite de 76 %). Sans egard a la FEVG, la survie sans evenement etait nettement meilleure chez les patients avec un ratio SLG/DM [less than or equal to] -0,2 %/ms (log-rank, p < 0,001). En conclusion, le ratio SLG/DM pourrait ameliorer la stratification du risque cardiovasculaire chez les sujets atteints d&apos;IC. [Traduit par la Redaction] Mots-cles : insuffisance cardiaque, arythmie ventriculaire maligne, stratification du risque cardiovasculaire, imagerie de strain 2D, strain longitudinal global, dispersion mecanique, ratio SLG/DM.

Introduction Coronary heart disease remains the leading cause of mortality and morbidity due to heart failure worldwide (Go et al. 2014). In the past decades, mitochondria have emerged as key [...], Monoamine oxidases (MAOs) have recently emerged as important mitochondrial sources of oxidative stress in the cardiovascular system. Generation of reactive oxygen species during the brief episodes of ischemic preconditioning (IPC) is responsible for the cardioprotection at reperfusion. The aim of this study was to assess the effects of two MAO inhibitors (clorgyline and pargyline) on the IPC-related protection in isolated rat hearts. Animals subjected to 30 min global ischemia and 120 min reperfusion were assigned to the following groups: (i) Control, no additional intervention; (ii) IPC, 3 cycles of 5 min ischemia and 5 min reperfusion before the index ischemia; (iii) IPC-clorgyline, IPC protocol bracketed for 5 min with clorgyline (50 µmol/L); (iv) IPC-pargyline, IPC protocol bracketed for 5 min with pargyline (0.5 mmol/L). The postischemic functional recovery was assessed by the left ventricular developed pressure (LVDP) and the indices of contractility (+dLVP/dt max) and relaxation (-dLVP/dt max). Infarct size (IS) was quantified by TTC staining. In both genders, IPC significantly improved functional recovery that was further enhanced in the presence of either clorgyline or pargyline. IS reduction was comparable among all the preconditioned groups, regardless of the presence of MAO inhibitors. In isolated rat hearts, acute inhibition of MAOs potentiates the IPC-induced postischemic functional recovery without interfering with the anti-necrotic protection. Key words: monoamine oxidase, MAO inhibitors, ischemic preconditioning, isolated rat heart. Les monoamine oxydases (MAOs) se sont recemment revelees d'importantes sources de stress oxydatif mitochondrial dans le systeme cardiovasculaire. La generation de derives reactifs de l'oxygene au cours d'episodes brefs de preconditionnement ischemique (PCI) est responsable de la cardioprotection lors de la reperfusion. La presente etude visait a evaluer les effets de deux inhibiteurs de la MAO (la clorgyline et la pargyline) sur le PCI dans un modele de caeur isole de rat. Nous avons soumis les animaux a une ischemie globale de 30 min, puis a une reperfusion de 120 min et les avons repartis dans les groupes suivants: (i) temoin (aucune intervention supplementaire), (ii) PCI (3 cycles de 5 min d'ischemie suivis de 5 min de reperfusion avant l'ischemie de reference), (iii) PCI-clorgyline (protocole de PCI alternant avec l'administration de clorgyline a 50 µmol/L pendant 5 min) et (iv) PCI-pargyline (protocole de PCI alternant avec l'administration de pargyline a 0,5 mmol/L pendant 5 min). Nous avons ensuite evalue le retablissement fonctionnel post-ischemique en mesurant la pression ventriculaire gauche developpee (PVGD) ainsi que les indices de contractilite (+dP/dt max) et de relaxation (-dP/dt max). Enfin, nous avons quantifie la taille de l'infarctus par la technique de coloration au TTC. Chez les animaux des deux sexes, le PCI a permis d'ameliorer clairement le retablissement fonctionnel qui a ete accentue en presence de clorgyline ou de pargyline. Par ailleurs, la diminution de la taille de l'infarctus etait comparable dans tous les groupes soumis au preconditionnement, et ce, sans egard a la presence d'inhibiteurs de la MAO. En somme, dans les caeurs isoles de rat, l'administration a court terme d'inhibiteurs de la MAO potentialise la recuperation fonctionnelle post-ischemique induite par le PCI, sans nuire a la protection contre la necrose. [Traduit par la Redaction] Mots-cles: monoamine-oxydase, inhibiteurs de la MAO, preconditionnement ischemique, caeur isole de rat.

Introduction In the past decades mitochondria have emerged as major contributors to the pathogenesis of myocardial ischemia/reperfusion (I/R) injury as well as important therapeutic targets in cardioprotection (Camara et al. [...], A substantial body of evidence indicates that pharmacological activation of mitochondrial ATP-sensitive potassium channels (m[K.sub.ATP]) in the heart is protective in conditions associated with ischemia/reperfusion injury. Several mechanisms have been postulated to be responsible for cardioprotection, including the modulation of mitochondrial respiratory function. The aim of the present study was to characterize the dose-dependent effects of novel synthetic benzopyran analogues, derived from a BMS-191095, a selective m[K.sub.ATP] opener, on mitochondrial respiration and reactive oxygen species (ROS) production in isolated rat heart mitochondria. Mitochondrial respiratory function was assessed by high-resolution respirometry, and [H.sub.2][O.sub.2] production was measured by the Amplex Red fluorescence assay. Four compounds, namely KL-1487, KL-1492, KL-1495, and KL-1507, applied in increasing concentrations (50, 75, 100, and 150 µmol/L, respectively) were investigated. When added in the last two concentrations, all compounds significantly increased State 2 and 4 respiratory rates, an effect that was not abolished by 5-hydroxydecanoate (5-HD, 100 µmol/L), the classic m[K.sub.ATP] inhibitor. The highest concentration also elicited an important decrease of the oxidative phosphorylation in a [K.sup.+] independent manner. Both concentrations of 100 and 150 µmol/L for KL-1487, KL-1492, and KL-1495, and the concentration of 150 µmol/L for KL-1507, respectively, mitigated the mitochondrial [H.sub.2][O.sub.2] release. In isolated rat heart mitochondria, the novel benzopyran analogues act as protonophoric uncouplers of oxidative phosphorylation and decrease the generation of reactive oxygen species in a dose-dependent manner. Key words: rat heart mitochondria, benzopyran analogues, protonophores, uncoupling, hydrogen peroxide. De plus en plus de donnees indiquent que l'activation pharmacologique des canaux potassiques sensibles a l'ATP de la mitochondrie (m[K.sub.ATP]) du coeur le protege lorsqu'il est expose a des conditions associees au dommage d'ischemie/reperfusion. Plusieurs mecanismes pourraient etre responsables de la cardioprotection incluant la modulation de la fonction respiratoire mitochondriale. Le but de l'etude presente etait de caracteriser les effets lies a la dose de nouveaux analogues synthetiques du benzopyrane, derives du BMS-191095, un compose qui ouvre selectivement les m[K.sub.ATP], sur la respiration mitochondriale et la production d'especes reactives d'oxygene (ERO) dans les mitochondries isolees du coeur de rat et ce. La fonction respiratoire mitochondriale a ete evaluee par respirometrie a haute resolution et la production de [H.sub.2][O.sub.2] a ete mesuree par un dosage en fluorescence a l'aide de la trousse Amplex Red. Quatre composes, a savoir KL-1487, KL-1492, KL-1495 et KL-1507, ajoutes en concentrations croissantes (50,75,100 et 150 µmol/L, respectivement), ont ete examines. Lorsqu'ajoutes aux deux concentrations les plus elevees, tous les composes accroissaient significativement les taux respiratoires aux etats 2 et 4, effet qui n'etait pas aboli par le 5-hydroxydecanoate (5-HD, 100 µmol/L), l'inhibiteur classique des m[K.sub.ATP]. La plus forte concentration induisait aussi une diminution importante de la phosphorylation oxydative de maniere independante du [K.sup.+]. Les deux concentrations de 100 µmol/L et 150 µmol/L de KL-1487, KL-1492 et KL-1495, et la concentration de 150 µmol/L de KL-1507 diminuaient respectivement la liberation de [H.sub.2][O.sub.2] de la mitochondrie. Les nouveaux analogues du benzopyrane agissent comme decouplants protonophores de la phosphorylation oxydative dans les mitochondries isolees du coeur de rat, et diminuent la generation d'especes reactives d'oxygene en fonction de leur concentration. [Traduit par la Redaction] Mots-cles : mitochondries du coeur de rat, analogues du benzopyrane, protonophores, effet decouplant, peroxyde d'hydrogene.

Introduction Diabetes mellitus (DM), the most severe metabolic disease associated with increased cardiovascular morbidity and mortality, is widely recognized nowadays as a serious threat to global health, owing to its [...], Diabetes mellitus (DM) is widely recognized as the most severe metabolic disease associated with increased cardiovascular morbidity and mortality. The generation of reactive oxygen species (ROS) is a major event causally linked to the development of cardiovascular complications throughout the evolution of DM. Recently, monoamine oxidases (MAOs) at the outer mitochondrial membrane, with 2 isoforms, MAO-A and MAO-B, have emerged as novel sources of constant hydrogen peroxide ([H.sub.2][O.sub.2]) production in the cardiovascular system via the oxidative deamination of biogenic amines and neurotransmitters. Whether MAOs are mediators of endothelial dysfunction in DM is unknown, and so we studied this in a streptozotocin-induced rat model of diabetes. MAO expression (mRNA and protein) was increased in both arterial samples and hearts isolated from the diabetic animals. Also, [H.sub.2][O.sub.2] production (ferrous oxidation--xylenol orange assay) in aortic samples was significantly increased, together with an impairment of endothelium-dependent relaxation (organ-bath studies). MAO inhibitors (clorgyline and selegiline) attenuated ROS production by 50% and partially normalized the endothelium-dependent relaxation in diseased vessels. In conclusion, MAOs, in particular the MAO-B isoform, are induced in aortas and hearts in the streptozotocin-induced diabetic rat model and contribute, via the generation of [H.sub.2][O.sub.2], to the endothelial dysfunction associated with experimental diabetes. Key words: monoamine oxidases, experimental diabetes mellitus, oxidative stress, endothelial dysfunction, clorgyline, selegiline. Il est largement accepte que le diabete sucre est la maladie metabolique la plus grave, associee a une morbidite et une mortalite cardiovasculares. La production de derives reactifs de l'oxygene (DRO) est une manifestation majeure entrainant des complications cardiovasculaires tout au long de la progression du diabete sucre. Recemment, les monoamine oxydases (MAO) de la membrane mitochondriale externe sous deux isoformes (MAO-A et MAO-B) se sont demarquees comme de nouvelles sources de production constante de peroxyde d'hydrogene ([H.sub.2][O.sub.2]) dans le systeme cardiovasculaire par l'intermediaire de la desamination oxydative des amines biogenes et des neurotransmetteurs. On ne sait pas si les MAO sont des mediateurs de la dysfonction endotheliale dans le diabete sucre, et c'est ce que nous avons etudie avec ce modele de diabete induit par la streptozotocine chez le rat. L'expression des MAO (ARNm et proteines) augmentait dans les echantillons arteriels comme dans les creurs isoles d'animaux diabetiques. De plus, la production de [H.sub.2][O.sub.2] (test de l'oxydation des ions ferreux revelee par le xylenol orange) dans des echantillons d'aorte etait nettement accrue et associee a un deficit de la relaxation dependante de l'endothelium (etudes en bain d'organe). L'administration des inhibiteurs des MAO (clorgyline et selegiline) a permis de diminuer la production de DRO de 50% et est parvenue en partie a retablir la relaxation dependante de l'endothelium a une valeur normale dans les vaisseaux atteints. En conclusion, dans le modele de diabete induit par la streptozotocine chez le rat, les MAO, en particulier l'isoforme MAO-B, sont induites dans les aortes et les creurs des animaux et contribuent par la production de [H.sub.2][O.sub.2] a la dysfonction endotheliale observee dans un modele experimental du diabete. [Traduit par la Redaction] Mots-cles: monoamine oxydases, diabete sucre experimental, stress oxydatif, dysfonction endotheliale, clorgyline, selegiline.