Atrial fibrillation is the most prevalent form of cardiac arrhythmia. Studies in animal modelshave provided important insights into arrhythmia mechanisms. However, to date, we do not dispose ofanimal models of spontaneous atrial arrhythmia.Thus, we aimed to develop a model of spontaneous atrial arrhythmia in rats and to assesspathophysiological mechanisms of these arrhythmias by using a multidisciplinary approach. We alsoaimed to assess the presence and the extent of inflammation and endothelial dysfunction, incriminatedin atrial fibrillation-related complications such as stroke, in atrial fibrillation patients.The animal study describes the first animal model of spontaneous atrial arrhythmias. We alsoprovide evidence that multiple mechanisms participate in arrhythmia occurrence in this model,particularly autonomic imbalance with relative vagal hyperactivity, left atrial endocardial fibrosis, anddecreased left atrial expression of the Pitx2 gene. In our clinical study, we found high levels ofvascular endothelial growth factor and von Willebrand factor in atrial fibrillation patients compared tosinus rhythm controls. These results suggest specific thromboembolic risk patterns according to theclinical form of arrhythmia and highlight a parallel evolution of atrial fibrillation and endothelialdysfunction. These results add new insights into the understanding of atrial arrhythmias. This new animalmodel could facilitate studies of pathophysiological mechanisms involved in atrial arrhythmias andallow assessment of efficacy and toxicity of therapeutic agents in a setting that faithfully reproducesthe clinical presentation of the arrhythmia
| Identifer | oai:union.ndltd.org:CCSD/oai:tel.archives-ouvertes.fr:tel-00933537 |
| Date | 26 October 2012 |
| Creators | Scridon, Alina |
| Publisher | Université Claude Bernard - Lyon I |
| Source Sets | CCSD theses-EN-ligne, France |
| Language | English |
| Detected Language | English |
| Type | PhD thesis |
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