UC San Diego

Cardiovascular disease is the primary cause of death in the United States and presents a significant challenge for researchers and clinicians due to the complexity and non-uniformity of structure-function relationships in the heart. The largest of the four heart chambers, the left ventricle, must pump efficiently and adapt to changes in demand or blood flow, which the normal heart does remarkably well. However, in disease states, the compensatory response of the myocardium and persistent overloading can cause remodeling to become counter-productive.

Two of the major diseases contributing to overall cardiac morbidity and mortality are hypertension and myocardial infarction. While much is understood about the forms of remodeling and the associated dysfunction that occur in these disease states, they are usually measured at the scale of the entire organ (e.g. ejection fraction), or only in a select region of tissue. Many studies have shown regional variations in structural properties in the normal heart, but a comprehensive understanding of regional remodeling and the resultant functional consequences in disease states is lacking. Thus, the primary aims of this dissertation are to:

1. Determine the effect of pressure overload on regional distributions of electrophysiological and calcium handling proteins in the rat left ventricle.

2. Test the hypothesis that regional gradients in structural properties such as myocyte geometry are diminished in pressure overload.

a. Determine whether regional variations in these structural features could be comprehensively and non-invasively quantified using DT-MRI.

3. Compare the measured size of a scar after myocardial infarction using traditional methods to the size of the corresponding region of dysfunction using a novel 3D MRI-based approach.

A better understanding of regional variations in normal and diseased ventricles will be valuable in identifying potential targets for therapeutic intervention to slow, prevent, or reverse adverse remodeling in patients with cardiac diseases such as hypertension or infarction, and provide insight as to the mechanisms by which regional variations contribute to overall pump function.