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We study this problem at multiple levels of integration from molecules and cells to abnormalities of heart rhythm in patients.
At a molecular level, they seek to understand how ion channel proteins perform their essential tasks, in particular they are interested in a key paradox how these channels permit the flow of millions of ions a second, yet do this with exquisite selectivity (sodium channels allow sodium ions but not similarly sized and charged potassium ions).
More recently they have turned their attention to the regulation of sodium and potassium channels by important cellular signaling systems which are involved in not only in how the heart conducts electricity but also the force with which it contracts.
The diseased heart undergoes a series of changes, initially compensatory but ultimately maladaptive, that increase the risk of potentially lethal arrhythmias. These changes are commonly referred to as remodeling. Dr. Tomaselli’s group is studying the remodeling process in animal models of heart failure using gene expression, protein and ionic current measurements. They have developed a canine microarray for the broad-based study of gene expression in the failing canine heart.
At the ultimate level of integration they are examining the role of implanted defibrillators (ICDs) in patients with diseased, remodeled hearts. They have initiated a study referred to as PROSe-ICD (PRospective Observational Study of the ICD in the prevention of sudden death).
PROSe-ICD has enrolled nearly 800 patients all have undergone detailed clinical and electrocardiographic studies as well as having blood collected for performing genetic and proteomic analyses. Over 25% of this cohort has undergone detailed cardiac imaging (MR and CT) and spectroscopy to identify imaging based markers of risk of sudden death. The overarching goal is to better understand the mechanisms of sudden arrhythmic death and to develop better predictors of risk of this devastating outcome.