Ciencias Exactas y Ciencias de la Salud

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Advisor: search.filters.advisor.García Rivas, Gerardo de JesúsSubject: search.filters.subject.Arrhythmia

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    The role of the mitochondrial calcium uniporter in the process of arrhythmogenesis in a murine model of acute catecholamine overload
    (Instituto Tecnológico y de Estudios Superiores de Monterrey, 2020-05-22) Salazar Ramírez, Felipe de Jesús; SALAZAR RAMIREZ, FELIPE DE JESUS; 876167; García Rivas, Gerardo de Jesús; emipsanchez; Alves Figueiredo, Hugo Jorge; Rojas Martínez, Augusto; Ramos Mondragón, Roberto; Escuela de Medicina y Ciencias de la Salud; Campus Monterrey
    Sudden cardiac death by fulminant ventricular arrhythmias remains a concern in population with cardiac risk. Recently, the mitochondrion has been implied to be a central player in Ca2+ mishandling, with its dysfunction leading up to arrhythmogenesis. A possible starting event that could lead to most changes seen in cardiac disfunction is mitochondrial Ca2+ overload. The following research study focuses on demonstrating the effects of mitochondrial Ca2+ influx inhibition in arrhythmogenesis. A murine model of acute catecholamine (isoproterenol) overload was treated previously with mitochondrial Ca2+ transport inhibitor Ru360. Ru360 treated mice showed a complete abolishment of ventricular tachycardia and ventricular fibrillation. To characterize the possible mechanisms of action, heart mitochondria were isolated and mitochondrial function was assessed. Mitochondrial Ca2+ transport inhibition preserved mitochondrial function and membrane integrity as demonstrated by a higher respiratory control and calcium retention capacity when compared to isoproterenol-treated mice which appears to be caused by a reduced oxidative stress as a trend to preserve reduced thiol groups was shown. Given the positive results obtained in abolishing ventricular arrhythmias by inhibiting mitochondrial Ca2+ transport, it is precise to continue the characterization of the mechanisms by which this therapy exerts its effects. To fully demonstrate its efficacy and characterize its mechanism of action may lead up to a new therapeutic target and therapy that could set the bases to clinical research in the near future.
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