Abstract 13110: Cardiac Overexpression of PPARgamma Induces Ion Channel and Connexin Remodeling Leading to Spontaneous Fatal Arrhythmias

Background: Diabetes and obesity, which confer an increased risk of sudden cardiac death, are associated with cardiac myocyte lipid accumulation and altered cardiac electrical properties, manifest by prolongation of the QRS duration and QT interval. It is difficult to distinguish the contribution of cardiomyocyte lipid accumulation versus the contribution of global metabolic defects to the increased incidence of sudden death and electrical abnormalities. Methods and Results: In order to study the effects of metabolic abnormalities on arrhythmias without the complex systemic effects of diabetes and obesity, we studied mice with cardiac-restricted overexpression of PPARgama, which causes the abnormal accumulation of intracellular lipids in cardiomyocytes. The PPARgamma mice die as young adults, prior to a significant reduction in systolic function. These mice have spontaneous ventricular tachyarrhythmias, secondary to reduced ventricular repolarization, caused by voltage-dependent K+ channel remodeling, spe...