9634974 McCulloch The heart is a complex three-dimensional muscular organ in which electrical signals trigger coordinated muscle contraction to produce the pumping action. Not only does the electrical system of the heart affect its mechanical pumping, but mechanics also affect the electrical system. The cause of these interactions has been studied in great detail at the level of the individual heart muscle cell. But understanding how these cellular properties affect the performance of the whole heart is made extremely difficult by the complex anatomy and structure of the heart wall. Such an understanding is essential if the new findings of cellular biological science are to be applied to the prevention and diagnosis of cardiac disease and the treatment of heart patients. Therefore, the objective of this research is to develop anatomically accurate computer models of the heart that are based soundly on the underlying physics and biology of the heart cells. To test these models, accurate measurements in careful experiments will be conducted. Building on our work over the past five years, we will conduct sophisticated new computer models of the heart using methods of analysis similar to those used in the automotive and aerospace industries. Our methods have been specialized to handle the unique complexities of cardiac biology. The models vi II be based on detailed new measurements of the shape and structure, mechanical, electrical and cellular properties of the heart wall. Because these models will be extremely demanding to even the fastest computers, we will run them on supercomputers at the San Diego Supercomputer Center. The completed computer models will be used to investigate unanswered questions about how the electromechanical properties of individual heart cells affect the performance of the whole heart. To test the reliability and accuracy of the computer models, new experimental methods will be developed for simultaneously studying electrical and mechanical properties in the heart. These measurements will be used to improve the models, which can then be extended to analyze interactions between mechanics and other physiological processes in the heart such as bloodflow. 'These new computer models will have diverse applications in cardiac physiology, in the bioengineering design of new cardiac diagnostic and treatment methods (such as cardiac ultrasound, MRI and pacemakers) and as simulation tools for education and training of doctors and patients, scientists, students and engineers. ***
