This application addressed broad challenge area (15), Translational Science, and specific Challenge topic 15-HL-103: Establish the infrastructure to obtain, in a standardized manner, diseased and healthy human cardiac tissue obtained at surgery for immediate electromechanical studies to further the fundamental understanding of cardiac rhythm and contractility. Current efforts into investigation of cardiac malfunction on both the electrical and mechanical level are hampered by the lack of fundamental information of human cardiac function. Although animal models have provided a wealth of information and understanding of the underlying pathobiology, data from these models cannot be unambiguously translated to the human situation. In order to ultimately treat human cardiopathological conditions via hypothesis-drive strategies, it is imperative that we obtain data on electrical and mechanical function in human tissue. In order to do so, it is critically important that this tissue be studied alive. It is long known that the dynamic situation of the cardiac beat, where ion concentrations, myofilament properties, and mechanical load are changing continuously during a beat, requires live cells for investigation. It is equally important that studies on such live human tissue are designed and executed in a fashion that optimizes the extrapolation of the data so obtained to the human in vivo/in situ situation. In line with the aim of the proposal, the overriding goal is to establish and use the infrastructure to obtain, in a standardized manner, diseased and healthy human cardiac tissue obtained at surgery for immediate electromechanical studies to further the fundamental understanding of cardiac rhythm and contractility. The overall success of the proposal hinges on both critical prerequisites as well as on critical achievements. The prerequisites needed are the availability of sufficient tissue on a regular basis, the infrastructure present to optimize the use of such tissue, and the expertise of the investigators to obtained quality and useful data. The critical achievements reside in the number and topical variety of investigators working with this tissue, the use of aligned and validated, standardized protocols, the completeness and quality execution of the assessments made and finally on the interpretation of the data obtained. To assure we meet these challenges, we have composed a team of field-leading experts in the study of live cell and live tissue aspects of cardiac electrophysiology and cardiac mechanics. The aligned protocols using state-of-the-art techniques and equipment, will lay the basis to obtain quality data sets of the highest achievable inclusion of electrical and contractile parameters of human cardiac function to date. This data is to be used by the entire clinical and research community to strategize novel treatment therapies, as well as form the basis for further hypothesis-driven studies and comprehensive computer modeling.
The goal of the project is to collect a comprehensive data set on the electrical and mechanical behavior of live human myocardium in health and disease. Studied in tissue explanted from human patients, by a large investigative e team of experts, we will learn crucial new information on how human myocardium (mis-)behaves functionally in health and disease, and use this data to strategize improved or novel treatment for patients with cardiac diseases.
