Arial fibrillation is the most common chronic arrhythmia afflicting 4% of the population over the age of 60 years. With aging of the population this incidence is going to increase. Serious complications such as emboli stroke and cerebral haemorrhage (as patients need to beanticoagulated) a high morbidity and mortality are associated with atria fibrillation with greatsocio-economic implications. Until today, however, there is no effective treatment of the arrhythmia. Chronic atria fibrillation grows more resistant to pharmacological and electricalcardioversion the longer it persists. In recent years it has been elucidated that during the time course after the initiation of the arrhythmia a complex remodelling of the atria takes place, which involves the electrical, contractile and structural properties. Electrical remodelling leads to a reduction in the atria effective refractory period and a shortening of the action potential. Contractile remodelling is characterized by a loss of 70% of atria contractile function leading to thrombus formation in the atria with the risk of emboli stroke if the thrombus dislodges. It has been shown that alteration in intracellular Ca2+ homeostasis and Ca2+ handling properties play a major role in the remodelling process. During atria fibrillation intracellular Ca2+ and Na+concentrations increase. Although major insights into the path physiology of atria fibrillation on the cellular level have been gained the actual changes in intracellular ion concentrations have never been directly measured. Changes in intracellular calcium handling strongly interact with intracellular Na+ and H+ homeostasis. Therefore this project addresses the changes in alterations in intracellular ion concentrations (Ca2+, Na+ and H+) and ion handling properties in two established animal models of atria fibrillation as well as in human tissue of patients with chronic atria fibrillation.
Field of science
- /medical and health sciences/basic medicine/physiology/homeostasis
- /medical and health sciences/basic medicine/neurology/stroke
- /natural sciences/chemical sciences/inorganic chemistry/inorganic compounds
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