Despite decades of intensive investigation, sudden death secondary to ventricular fibrillation (VF) remains a leading cause of mortality in the US and other developed countries. Recently, several promising hypotheses regarding the mechanism for VF have been introduced. However, it has not been possible using currently available experimental techniques to determine which theory (or theories) is most applicable to VF. To address this issue, we propose to: 1) construct a cardiac mapping system from nanofabricated components that is capable of assessing cardiac activation and repolarization with high spatial and temporal resolution and with minimal tissue damage; 2) use a novel phase mapping technique to analyze the mapping data, with the objective of identifying the location and number of phase singularities during sinus rhythm, ventricular tachycardia and VF; 3) use the phase singularity data to distinguish between three putative mechanisms for VF - an anchored rotor with fibrillatory conduction, a meandering rotor or multiple rotors. MEMs technology will be used to construct microscale mechanical needle-like structures with integrated electrodes that are ultrasonically activated, to minimize tissue damage during insertion. The electrode arrays will be used to map activation and repolarization in canine ventricular myocardium in vitro and in normal and acutely ischemic pig hearts in situ during fixed pacing and during VF. The mapping data will be analyzed using a fast Fourier-demodulation technique to identify singularities and wave vectors during VF. Computer models of 2- and 3-D myocardium also will be used to generate surrogate data sets for testing the analysis algorithms. The results of this study will lead to significant advances in three key areas: development of devices to map cardiac electrical activity with unprecedented spatial resolution; application of newer and more sophisticated techniques to analyze large mapping data sets; interpretation of high resolution mapping data within the context of novel hypotheses regarding the genesis of ventricular tachycardia and fibrillation. Taken together, these advances in data acquisition, analysis and interpretation are expected to lead to new and more effective means of identifying and treating patients at risk for the development of lethal ventricular tachyarrhythmias. ? ? ? ? ?
| Cherry, Elizabeth M; Fenton, Flavio H; Gilmour Jr, Robert F (2012) Mechanisms of ventricular arrhythmias: a dynamical systems-based perspective. Am J Physiol Heart Circ Physiol 302:H2451-63 |
| Luther, Stefan; Fenton, Flavio H; Kornreich, Bruce G et al. (2011) Low-energy control of electrical turbulence in the heart. Nature 475:235-9 |
| Krogh-Madsen, Trine; Karma, Alain; Riccio, Mark L et al. (2010) Off-site control of repolarization alternans in cardiac fibers. Phys Rev E Stat Nonlin Soft Matter Phys 81:011915 |
| Fenton, Flavio H; Luther, Stefan; Cherry, Elizabeth M et al. (2009) Termination of atrial fibrillation using pulsed low-energy far-field stimulation. Circulation 120:467-76 |
| Krogh-Madsen, Trine; Christini, David J (2007) Action potential duration dispersion and alternans in simulated heterogeneous cardiac tissue with a structural barrier. Biophys J 92:1138-49 |
| Gilmour Jr, Robert F; Gelzer, Anna R; Otani, Niels F (2007) Cardiac electrical dynamics: maximizing dynamical heterogeneity. J Electrocardiol 40:S51-5 |
| Pumir, A; Nikolski, V; Horning, M et al. (2007) Wave emission from heterogeneities opens a way to controlling chaos in the heart. Phys Rev Lett 99:208101 |
| Lu, Sheng; Gong, Yunfan; Iwai, Sei et al. (2006) Structural barrier increases QT-peak dispersion in swine left ventricle in vivo. Conf Proc IEEE Eng Med Biol Soc 1:4039-42 |
