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Cardiac Metabolism: Engineering Methods for Analysis & Intervention Open Access

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The heart is an efficient machine capable of transducing chemical energy into mechanical pumping. Since the heart is accountable for its own perfusion, metabolism and mechanical function are intricately linked in both directions. In cardiac disease, a detriment in either metabolism or mechanics can quickly lead to the collapse of the other. An increased prevalence of cardiac disease in society has called for a clinical need for minimally invasive metabolic interventions: to reverse metabolic dysfunction and restore normal mechanics. This dissertation presents experimental evidence encompassing the effects of dichloroacetate, a compound shown to increase cardiac post-ischemic performance by reversing metabolically rooted impairment. The investigation includes the effect of dichloroacetate on the isolated heart not only before and after myocardial ischemia, but also under normoxic conditions without the confounding variable of hypoxia. Cardiac optical mapping was employed in order to better understand the action of dichloroacetate on function and metabolism. While laying an important foundation, several flaws of ubiquitous cardiac imaging techniques provided the inspiration for the engineering aspects of this dissertation: development and improvement of imaging methods to evaluate whole heart metabolism. For the first time, I present fluorescence recovery after photobleaching of the NADH molecule in the whole heart, a measure of metabolic activity. Additionally, I present selectivity analysis for mitochondrial spectrophotometric multicomponent predictions, which can be used to study cardiac metabolism with a high degree of accuracy and resolution.

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