Manfredi, Thomas [faculty advisor, Department of Kinesiology]
Heart failure; medical research; animal model; health
Heart failure (HF) is a condition in which the working heart is unable to meet the blood flow demands of the body. It is the leading cause of early death in the United States and is a progressive, debilitating disease that presently, can only be detected in late, irreversible stages. The progression of HF is complex and poorly understood, involving a number of molecular mechanisms. It is characterized by a complex of symptoms including cardiac hypertrophy and a shift in myocardial substrate utilization, all leading to reduced pumping efficiency of the heart and decreased systemic blood flow. In HF, the failing myocardium becomes more reliant on glucose as a fuel. In contrast, the healthy heart uses fatty acids almost exclusively to meet its energy requirements. The shift to glucose as a predominant fuel is indicative of many dynamic and molecular changes in the heart as HF progresses and is key toward identifying, characterizing, treating and potentially preventing early stage heart failure.
The animal model of HF is a vital research tool, allowing for investigation in systems that are physiologically very similar to that of the human. Despite the research challenges caused by the small heart size, mouse models are particularly desirable because they allow for genetic modification and have a rapid reproductive cycle. In this project an albumin perfused murine model was used to imitate the physiological profile of the human heart.
The goal of this project was to identify and characterize, in an albumin and fatty acid perfused working mouse heart, left ventricular end diastolic pressure and volume relationships and corresponding rates of myocardial glycolysis and fatty acid oxidation. The exploration of dynamic measures of cardiac physiology in concert with substrate metabolism in a model that closely mimics the human physiological system shows great promise for future research and development of clinical diagnostic tools and novel therapeutic interventions for the prevention or attenuation of heart failure. This novel project, utilizing the albumin and fatty acid perfused working mouse heart lays the groundwork for future investigations of the dynamic and metabolic aspects of HF.