There are currently 5 million Americans with diagnosed heart failure, and 550,000 new cases every year. Heart failure causes significant morbidity and mortality from the mechanical dysfunction itself as well as from arrhythmias. Human studies aimed at studying the mechanisms of regulation (and dysregulation) of excitation contraction coupling and arrhythmia substrates are limited, and currently there is a large gap between what is known about cardiovascular diseases and arrhythmias in animals as opposed to humans. This proposal attempts to close this gap by creating a system of acquiring viable human failing and non-failing hearts and then quickly distributing the tissue and cells to researchers to perform experiments requiring """"""""live"""""""" preparations.
The Specific Aims that are proposed in this grant are designed to 1) develop the infrastructure to rapidly procure, preserve and distribute explanted human hearts for physiologic studies;2) To provide a resource of preserved human cardiac tissue to support several ongoing studies in electrophysiology and mechanical function requiring """"""""live"""""""" human cardiac tissue by several investigators. In order to achieve these aims, we will develop an """"""""on call"""""""" system of tissue collection, recruit and train the personnel needed to collect the tissue such that viability is maintained, and distribute viable tissue to researchers for experiments. In addition, a web based database will be developed to identify researchers needing tissue, be able to notify those researchers that tissue is available, and provide background information about the tissue. By obtaining viable failing and non-failing human hearts, several areas will be addressed with hypothesis driven research. These areas include: mechanisms of cardiac arrhythmias, electrophysiological properties of cardiac tissue, adrenergic receptors and signal transduction, connexin expression and trafficking, intracellular calcium handling, and ventricular function in diseased hearts. There are several laboratories within the University of California system including UCSF and UC Davis performing these areas of cardiovascular research that would benefit from having the ability to acquire viable human tissue. This research will be able to paint a broad stroke of advancement in cardiovascular research as for the first time,several hypothesis driven studies will be able to be performed using human tissue.
Heart failure is a significant health issue in the United States, and most of what is known about heart failure and the other cardiovascular problems that are associated with it has come from animal studies. With this grant we will be able to continue to develop a resource of human heart tissue for investigators to perform experiments to further understand the mechanisms of these cardiovascular problems.
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| Rahmutula, Dolkun; Marcus, Gregory M; Wilson, Emily E et al. (2013) Molecular basis of selective atrial fibrosis due to overexpression of transforming growth factor-?1. Cardiovasc Res 99:769-79 |
