Treatments aimed at modifying cardiac substrate utilisation are designed to improve metabolic efficiency. In the fasting state, the heart mainly relies on fatty acid oxidation for its energy production. The heart can adapt to metabolise glucose, lactate and amino acids depending on the predominate milieu and demands placed upon it. A shift from fatty acid oxidation to carbohydrate oxidation leads to a lower oxygen consumption per unit of adenosine triphosphate produced. It is this concept of improving cardiac efficiency by a reduction in oxygen demand that underpins the use of metabolic manipulating agents as a therapeutic strategy in heart failure. Cardiac energy starvation is increasingly recognised as playing a central role in the pathophysiology of heart failure. Alterations in substrate utilisation thus underlie the hope that metabolic manipulating agents will be of benefit in heart failure of both ischaemic and non-ischaemic origin. This metabolic shift is achieved by promoting glucose utilisation and reducing the utilisation of fatty acids. This leads to a greater production of adenosine triphosphate per unit of oxygen consumed. With an ongoing demand for treatment options in ischaemic heart disease and the growing burden of chronic heart failure, new treatment modalities beyond contemporary therapy warrant consideration. This thesis aims to investigate the short term effects of metabolic manipulation on changes in cardiac energetic status, cardiac function, efficiency and substrate utilisation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:577622 |
| Date | January 2013 |
| Creators | Beadle, Roger |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=201651 |
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