Mitochondrial Dysfunction as an Arrhythmogenic Substrate A Translational Proof-of-Concept Study in Patients With Metabolic Syndrome in Whom Post-Operative Atrial Fibrillation Develops

ObjectivesThis study sought to provide bedside evidence of the potential link between cardiac mitochondrial dysfunction and arrhythmia as reported in bench studies.BackgroundAtrial fibrillation (AF) is a frequent complication of cardiac surgery. Underlying mechanisms of post-operative atrial fibrillation (POAF) remain largely unknown. Because cardiac mitochondrial dysfunction has been reported in clinical conditions with a high risk of POAF, we investigated whether a causal link exists between POAF onset and pre-operative function of cardiac mitochondria.MethodsPre-operative mitochondrial respiration and calcium retention capacity, respiratory complex activity, and myocardial oxidative stress were quantified in right atrial tissue from 104 consecutive patients with metabolic syndrome, in sinus rhythm, and undergoing coronary artery bypass graft surgery.ResultsIn this high-risk population, POAF occurred in 44% of patients. Decreased pre-operative mitochondrial respiration and increased sensitivity to calcium-induced mitochondrial permeability transition pore opening were significantly associated with POAF. Adenosine diphosphate–stimulated mitochondrial respiration supported by palmitoyl-l-carnitine was significantly lower in POAF patients and remained independently associated with AF onset after adjustment for age, body mass index, heart rate, beta-blocker use, and statin medication (multivariate logistic regression coefficient per unit = −0.314 ± 0.144; p = 0.028). Gene expression profile analysis identified a general downregulation of the mitochondria/oxidative phosphorylation gene cluster in pre-operative atrial tissue of patients in whom AF developed.ConclusionsOur prospective study identifies an association between pre-operative mitochondrial dysfunction of the atrial myocardium and AF occurrence after cardiac surgery in patients with metabolic disease, providing novel insights into the link between mitochondria and arrhythmias in patients

Suffering and the law

La souffrance a une faculté de nuisance : elle affaiblit l’être, accapare ses pensées et contribue à son isolement. Le droit a intérêt à appréhender ce sentiment, car il est un danger pour l’homme dont la capacité d’action est menacée, et pour la collectivité dont la cohésion est fragilisée par la mise à l’écart du souffrant. C’est dans la réaction et dans la lutte que le droit appréhende la souffrance. Il a réagi à la souffrance infligée à autrui en accordant à la victime une indemnité compensatrice et, par le progrès des techniques médicales, s’est enrichi de dispositifs destinés à l’éliminer. La souffrance présente deux aspects : l’ « avoir mal », qui est une crise de la sensibilité, et l’ « être mal », qui est une crise existentielle. En droit civil de la réparation comme en droit médical, le fait d’avoir mal a été pris en considération avant le mal-être des hommes, le droit ayant tenu compte de ce dernier en raison d’une préoccupation nouvelle des hommes pour leur bien-être. L’étude de l’ « avoir mal » montre que le droit s’est attaché à réparer les souffrances injustement subies et, venant se placer aux côtés de la médecine, à les soulager en permettant le recours à des moyens techniques et humains. Quant au mal-être, il est de nos jours réparé lorsqu’il est injustement subi, et des mesures symboliques permettent d’apaiser ceux qui en souffrent. Des dispositifs favorisent aussi son élimination par le recours aux techniques médicales, mais le souci croissant de satisfaire les demandes individuelles en n’imposant plus la preuve d’une pathologie, questionne la vocation thérapeutique du droitSuffering has the capacity to do harm. It weakens men, monopolizes their thoughts, and isolates them. The law must apprehend this feeling because it is dangerous for individuals as well as society, which loses one of its own. The law apprehends suffering through reaction and struggle. It provides compensation to the victim who suffers unjustly. It acts directly against suffering by allowing medical techniques to be used to eliminate it. Suffering has two aspects: pain and ill-being. In civil and medical law, pain was considered before ill-being. The latter was taken into account because of a new concern for well-being. The study of pain shows that the law has endeavoured to repair it, and, by assisting medicine, to relieve it by authorizing the use of medical techniques. In the same way, ill-being is today repaired when it is unjustly suffered, and symbolic measures make it possible to appease those who suffer from it. Laws also allow its elimination through the use of medical techniques. However, the desire to satisfy the people's demands by no longer imposing the proof of a disease questions the therapeutic vocation of the law. In any case, pain and ill-being can’t be apprehended in the same way because they are of a different nature. This work has shown that suffering is a complex feeling, that law has difficulties in apprehending it, and that the context in which our society evolves has an influence. It also warns against the technique which can be the object of misus

L'interdit de tuer

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L'interdit de tuer

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Le choix du traitement médical : dialogue entre juristes, psychologues et philosophe

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Ridge optical waveguide curved in a KTiOPO4 single crystal for triple photon generation: preliminary characterization by birefringence phase-matched third-harmonic generation

International audienceRidge waveguides carved in bulk nonlinear crystals such as KTiOPO4 (KTP) are used to reach a strong confinement of electromagnetic waves with large second-order or third-order non-linearity. We report on our recent experiments where we show the possibility to shape the birefringence phase-matching (BPM) conditions for direct Third-Harmonic Generation (THG: ω + ω + ω → 3ω) in micrometric KTP ridge waveguides by acting on their transverse dimensions. The real goal of this preliminary study is to design quantum optical experiments based on Triple Photons Generation (TPG: 3ω → ω + ω + ω) that is the reverse process of THG, thus exhibiting the same BPM conditions

Ridge optical waveguide curved in a KTiOPO4 single crystal for triple photon generation: preliminary characterization by birefringence phase-matched third-harmonic generation

International audienceRidge waveguides carved in bulk nonlinear crystals such as KTiOPO4 (KTP) are used to reach a strong confinement of electromagnetic waves with large second-order or third-order non-linearity. We report on our recent experiments where we show the possibility to shape the birefringence phase-matching (BPM) conditions for direct Third-Harmonic Generation (THG: ω + ω + ω → 3ω) in micrometric KTP ridge waveguides by acting on their transverse dimensions. The real goal of this preliminary study is to design quantum optical experiments based on Triple Photons Generation (TPG: 3ω → ω + ω + ω) that is the reverse process of THG, thus exhibiting the same BPM conditions

Ridge optical waveguide curved in a KTiOPO4 single crystal for triple photon generation: preliminary characterization by birefringence phase-matched third-harmonic generation

International audienceRidge waveguides carved in bulk nonlinear crystals such as KTiOPO4 (KTP) are used to reach a strong confinement of electromagnetic waves with large second-order or third-order non-linearity. We report on our recent experiments where we show the possibility to shape the birefringence phase-matching (BPM) conditions for direct Third-Harmonic Generation (THG: ω + ω + ω → 3ω) in micrometric KTP ridge waveguides by acting on their transverse dimensions. The real goal of this preliminary study is to design quantum optical experiments based on Triple Photons Generation (TPG: 3ω → ω + ω + ω) that is the reverse process of THG, thus exhibiting the same BPM conditions

A flux grown KTP crystal ridge optical waveguide for birefringence phase-matched second-harmonic generation

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