Multiscale Modeling of Myocardial Electrical Activity: From Cell to Organ

Cardiac arrhythmias represent a leading cause of morbidity and mortality in developed countries. In spite of intense research, the mechanisms of generation, maintenance and termination of theses arrhythmias are still not clearly understood. The ability to predict, prevent and treat these arrhythmias remains a major scientific challenge. In the last years, new technologies have produced a huge amount of information at different levels: subcellular, cellular, tissue, organ and system. However, the knowledge of each component is not sufficient by itself to understand its behavior and an integrative approach, which should take into account the complex interactions between all components is needed. This understanding is necessary to improve prevention and treatment of cardiac arrhythmias. Traditionally, cardiac research has been based on experimental and clinical studies. However, in the last decades, a quantitative understanding of the biophysical and biochemical properties of individual cardiac myocytes and of the anatomical structure of the heart has permitted the development of computational models of single myocytes, portions of tissue and even the whole heart. These models have opened a new approach in studying the complex mechanisms underlying cardiac arrhythmias by means of computer simulations. Integrated and multiscale models of the heart are improving very fast, as a large body of research is being made in this field. These models integrate, with a great degree of detail, the different levels of the organ, from the genetic characteristics of membrane ionic channels, to the electrophysiological characteristics of cardiac cells and to the anatomical structure of the different cardiac tissues. In this chapter, the basis of cardiac multiscale modeling will be reviewed and recent and specific case studies for the different levels will be described focusing on the understanding of cardiac arrhythmias during myocardial ischemia and drug treatment.