Florey Department of Neuroscience and Mental Health - Theses

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    Role of the area postrema in heart failure
    Abukar, Yonis ( 2017)
    Cardiovascular disease is the leading cause of death worldwide and one of the most debilitating diseases within this group is heart failure. Clinical studies indicate that heart failure is associated with increased sympathetic drive to various organs, but the exact mechanisms responsible are not known. A major area of focus for medical researchers is to establish the central mechanisms responsible for the increase in sympathetic nerve activity in heart failure. Particularly, there is intense interest in the increase of cardiac sympathetic nerve activity (CSNA) due to evidence that increased CSNA is a strong predictor of mortality in heart failure. My PhD studies tested the hypothesis that an increase in activity of central autonomic brain regions is responsible for the detrimental increase in sympathetic nerve activity to the heart during heart failure. Utilising a rodent as well as a large animal model of heart failure, I have investigated the role of the area postrema, a circumventricular organ, in modulating the increased CSNA during heart failure. My findings show that after lesion of the area postrema in sheep with heart failure, there was a significant reduction in the increased CSNA. Furthermore, in the rodent model of HF, the area postrema lesion prevented an increase in left ventricular end-diastolic pressure and a reduction in ejection fraction. These findings indicate an important role for the area postrema in modulating both increased CSNA as well as adverse heart function during heart failure. These findings have been presented at national and international conferences and the resulting manuscripts are currently under review.