RESUMO
Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration. Two important deleterious features are a Ca2+ dysregulation linked to Ca2+ influxes associated with ryanodine receptor hyperactivation, and a muscular nicotinamide adenine dinucleotide (NAD+ ) deficit. Here, we identified that deletion in mdx mice of CD38, a NAD+ glycohydrolase-producing modulators of Ca2+ signaling, led to a fully restored heart function and structure, with skeletal muscle performance improvements, associated with a reduction in inflammation and senescence markers. Muscle NAD+ levels were also fully restored, while the levels of the two main products of CD38, nicotinamide and ADP-ribose, were reduced, in heart, diaphragm, and limb. In cardiomyocytes from mdx/CD38-/- mice, the pathological spontaneous Ca2+ activity was reduced, as well as in myotubes from DMD patients treated with isatuximab (SARCLISA® ) a monoclonal anti-CD38 antibody. Finally, treatment of mdx and utrophin-dystrophin-deficient (mdx/utr-/- ) mice with CD38 inhibitors resulted in improved skeletal muscle performances. Thus, we demonstrate that CD38 actively contributes to DMD physiopathology. We propose that a selective anti-CD38 therapeutic intervention could be highly relevant to develop for DMD patients.
Assuntos
Distrofia Muscular de Duchenne , ADP-Ribosil Ciclase 1 , Animais , Humanos , Camundongos , Camundongos Endogâmicos mdx , Músculo Esquelético , Distrofia Muscular de Duchenne/genética , Miócitos Cardíacos/patologia , NAD/genética , NAD/uso terapêutico , NAD+ Nucleosidase/genética , FenótipoRESUMO
In cardiac surgery, patients are at risk of phrenic nerve injury, which leads to diaphragm dysfunction and acute respiratory failure. Diaphragm dysfunction (DD) is relatively frequent in cardiac surgery and particularly affects patients after coronary artery bypass graft. The onset of DD affects patients' prognosis in term of weaning from mechanical ventilation and hospital length of stay. The authors present a narrative review about diaphragm physiology, techniques used to assess diaphragm function, and the clinical application of diaphragm ultrasound in patients undergoing cardiac surgery.
RESUMO
Diaphragm ultrasound is a noninvasive technique that can be used to assess diaphragm function. In cardiac surgery, the technique may help physicians during the weaning process, in addition with echocardiography after surgery.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Diafragma , Estudos de Coortes , Ecocardiografia , UltrassonografiaRESUMO
Percutaneous extracorporeal membrane oxygenation is an invasive technique that provides emergent circulatory support for patients with cardiogenic shock. We report a favorable outcome of an acute fulminant myocarditis in a 25-year-old myasthenia patient with cardiogenic shock supported by percutaneous extracorporeal membrane oxygenation.
Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Miocardite/complicações , Choque Cardiogênico/terapia , Adulto , Biópsia , Ecocardiografia , Seguimentos , Humanos , Masculino , Miastenia Gravis/complicações , Miastenia Gravis/terapia , Miocardite/patologia , Miocardite/terapia , Miocárdio/patologia , Choque Cardiogênico/etiologia , Choque Cardiogênico/patologiaRESUMO
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by the absence of dystrophin, a sarcolemmal protein which links the cytoskeleton to the extracellular matrix by interacting with a large number of proteins. Heart failure is a classic complication of this disease. The authors review the pathogenesis and therapeutics of cardiac involvement in DMD.
Assuntos
Cardiomiopatias/genética , Cardiomiopatias/terapia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/terapia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Biomarcadores/metabolismo , Estimulação Cardíaca Artificial/métodos , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Quimioterapia Combinada , Distrofina/biossíntese , Distrofina/genética , Terapia Genética/métodos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Humanos , Distrofia Muscular de Duchenne/complicações , Distrofia Muscular de Duchenne/metabolismo , Guias de Prática Clínica como Assunto , Prognóstico , Transplante de Células-Tronco/métodos , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
Myotonic dystrophy type 1 (Steinert's disease) is a multisystem disorder with autosomal dominant inheritance. This disease is associated with the presence of an abnormal expansion of a cytosine thymine-guanine (CTG) trinucleotide repeat on chromosome 19q13.3. Because of rhythmic complications, the place for systematic electrophysiological study (EPS) has to be discussed.