Sudden cardiac death due to ventricular fibrillation (VF) is an important public health problem. However, our understanding of VF is limited. The broad, long-term objective of this research project is to elucidate the mechanisms of the generation and the maintenance of reentrant wavefronts in VF. The applicant has previously reported that the reentrant wavefronts are responsible for the generation VF in the canine model. In this grant application, the applicant proposes to study the reentrant wavefronts in VF both in vivo and in vitro. Computerized mapping studies will be performed in human patients and in dogs to document that reentrant wavefronts are present in Wiggers' stage II VF. Computerized mapping techniques and standard transmembrane microelectrode recording techniques will be used to study a novel in vitro model of sustained reentry. The following hypotheses will be tested: (1) Multiple reentrant wavefronts are present during Wiggers' stage II VF in humans, in normal healthy dogs, and in acutely ischemic dogs. (2) The reentrant wavefront circulates around an area of functional conduction block (the 'core' of reentry) formed by cells undergoing graded responses but not full action potentials. There is no anatomical barrier at the core of reentry. (3) In normal tissue, the cycle length of the reentrant wavefront is longer than the wavelength of the reentrant wavefront. Therefore, an excitable gap is present. (4) The size of the core and the duration of the excitable gap are both important in determining the generation and maintenance of reentry. (5) Perturbations that decrease the size of the core decrease the volume of tissue that is needed to support a reentrant wavefront. Therefore, the smaller the size of the core, the easier to induce multiple reentrant wavefronts and VF. (6) Perturbations that decrease the excitable gap can protect the reentrant wavefronts from termination by competing wavefronts. Therefore, the smaller the excitable gap, the longer the life-span of the reentrant wavefronts, and the easier for VF to sustain itself. (7) The size of the core and the excitable gap of the reentrant wavefronts are both decreased by ischemia, predisposing the heart to ventricular fibrillation in this setting. These studies will further our understanding of the basic mechanisms of the generation and maintenance of VF in humans, and lead to new insights into prevention and treatment of sudden cardiac death.
| de Diego, Carlos; Chen, Fuhua; Xie, Yuanfang et al. (2011) Anisotropic conduction block and reentry in neonatal rat ventricular myocyte monolayers. Am J Physiol Heart Circ Physiol 300:H271-8 |
| Liu, Yen-Bin; Lee, Yuan-Teh; Pak, Hui-Nam et al. (2009) Effects of simvastatin on cardiac neural and electrophysiologic remodeling in rabbits with hypercholesterolemia. Heart Rhythm 6:69-75 |
| Weiss, James N (2008) Beyond the implantable cardioverter-defibrillator: are we making progress? Heart Rhythm 5:S45-7 |
| Swissa, Moshe; Zhou, Shengmei; Tan, Alex Y et al. (2008) Atrial sympathetic and parasympathetic nerve sprouting and hyperinnervation induced by subthreshold electrical stimulation of the left stellate ganglion in normal dogs. Cardiovasc Pathol 17:303-8 |
| de Diego, Carlos; Chen, Fuhua; Xie, Lai-Hua et al. (2008) Cardiac alternans in embryonic mouse ventricles. Am J Physiol Heart Circ Physiol 294:H433-40 |
| Wu, Tsu-Juey; Lin, Shien-Fong; Hsieh, Yu-Cheng et al. (2008) Early recurrence of ventricular fibrillation after successful defibrillation during prolonged global ischemia in isolated rabbit hearts. J Cardiovasc Electrophysiol 19:203-10 |
| de Diego, Carlos; Pai, Rakesh K; Dave, Amish S et al. (2008) Spatially discordant alternans in cardiomyocyte monolayers. Am J Physiol Heart Circ Physiol 294:H1417-25 |
| Hayashi, Hideki; Shiferaw, Yohannes; Sato, Daisuke et al. (2007) Dynamic origin of spatially discordant alternans in cardiac tissue. Biophys J 92:448-60 |
| Tan, Alex Y; Chen, Peng-Sheng; Chen, Lan S et al. (2007) Autonomic nerves in pulmonary veins. Heart Rhythm 4:S57-60 |
| Chen, Peng-Sheng; Tan, Alex Y (2007) Autonomic nerve activity and atrial fibrillation. Heart Rhythm 4:S61-4 |
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