“Of mice and men – Insight into cardiac arrhythmia from human myocyte computational models”
Electrically based syndromes, such as cardiac arrhythmia, are multifactorial disorders that result in disruption of the normal electrical (and contractile) behavior of the heart. Cardiac arrhythmia is the most common cause of sudden cardiac death, and accounts for over 300,000 deaths per year in the United States alone. However, despite decades of extensive research, the underlying mechanisms of arrhythmia remain elusive and poorly defined. This may be due, in part, to reductionist approaches that study individual components of the cardiac electrical system in isolation and fail to capture altered protein and cellular interactions that cause rhythm derangements and abnormal contraction. Major difficulties lie in the complexity and nonlinearity of the cardiac system, which spans different spatial and temporal scales, and species-specificity of several electrophysiological processes, which often precludes translation of the results obtained in animal models to humans. To achieve an integrative understanding of such a complex system we utilize mathematical modeling and simulation to construct quantitative representations of human heart cell function in health and common widespread diseases, such as heart failure and atrial fibrillation. In this seminar, I will discuss how these developed frameworks allow accurate prediction of disease mechanisms, lend insight into the origins of clinical observations, and aid the identification of pro-arrhythmic targets. Furthermore, these models serve as platforms for the testing of pharmacological interventions to guide therapeutic strategies.