): The central goal of the project is to clarify the mechanisms by which ventricular fibrillation (VF) is maintained.
Specific Aim 1 will determine how agents that uncouple excitation-contraction like diacetyl monoxime (DAM) or cytochalasin D (cyto-D) and/or the voltage-sensitive dye affect VF activation patterns. The effects of these mechanical uncoupling drugs will be examined by mapping pig hearts with surface electrogram recordings 1) in situ, 2) in isolated perfused hearts, 3) isolated perfused hearts with uncoupling drugs and 4) isolated and perfused hearts with uncoupling drugs and voltage sensitive dyes.
Specific Aim 2 will correlate the regions of propagation block during VF with static and dynamic repolarization properties. The study will determine if propagation block in optical mapping data of VF correlate with 1) areas of non-uniform dispersion of intrinsic action potential duration (APD) and 2) if rate-dependent repolarization instabilities cause APD oscillations of growing amplitude that eventually lead to block in VF.
Specific Aim 3 will determine the prevalent mode of propagation during VF and its relationship to block. The applicant will develop a method to record a complete epicardial map of activation using 2 cameras as in """"""""Panoramic Mapping"""""""" and will use novel algorithms to unambiguously characterize activation arising from (1) rotors, (2) wandering wavelets or (3) epicardial breakthrough. The data will differentiate between alternate hypothesized VF mechanisms. The project will test hypotheses relating block to the drift of rotors and the interaction of intramural reentry with the epicardial surface.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL064184-01A1
Application #
6194786
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
2000-09-30
Project End
2003-08-30
Budget Start
2000-09-30
Budget End
2001-08-30
Support Year
1
Fiscal Year
2000
Total Cost
$215,250
Indirect Cost
Name
University of Alabama Birmingham
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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Bourgeois, Elliot B; Reeves, Hugh D; Walcott, Gregory P et al. (2012) Panoramic optical mapping shows wavebreak at a consistent anatomical site at the onset of ventricular fibrillation. Cardiovasc Res 93:272-9
Bourgeois, Elliot B; Bachtel, Andrew D; Huang, Jian et al. (2011) Simultaneous optical mapping of transmembrane potential and wall motion in isolated, perfused whole hearts. J Biomed Opt 16:096020
Bachtel, Andrew D; Gray, Richard A; Stohlman, Jayna M et al. (2011) A novel approach to dual excitation ratiometric optical mapping of cardiac action potentials with di-4-ANEPPS using pulsed LED excitation. IEEE Trans Biomed Eng 58:2120-6
Bourgeois, Elliot B; Fast, Vladimir G; Collins, Rueben L et al. (2009) Change in conduction velocity due to fiber curvature in cultured neonatal rat ventricular myocytes. IEEE Trans Biomed Eng 56:855-61
Dosdall, Derek J; Tabereaux, Paul B; Kim, Jong J et al. (2008) Chemical ablation of the Purkinje system causes early termination and activation rate slowing of long-duration ventricular fibrillation in dogs. Am J Physiol Heart Circ Physiol 295:H883-9
Rogers, J M; Walcott, G P; Gladden, J D et al. (2008) Epicardial wavefronts arise from widely distributed transient sources during ventricular fibrillation in the isolated swine heart. New J Phys 10:nihpa48217
Tabereaux, Paul B; Walcott, Greg P; Rogers, Jack M et al. (2007) Activation patterns of Purkinje fibers during long-duration ventricular fibrillation in an isolated canine heart model. Circulation 116:1113-9
Rogers, Jack M; Walcott, Gregory P; Gladden, James D et al. (2007) Panoramic optical mapping reveals continuous epicardial reentry during ventricular fibrillation in the isolated swine heart. Biophys J 92:1090-5
Kay, Matthew W; Walcott, Gregory P; Gladden, James D et al. (2006) Lifetimes of epicardial rotors in panoramic optical maps of fibrillating swine ventricles. Am J Physiol Heart Circ Physiol 291:H1935-41

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