An electric defibrillation shock is the only effective therapy to halt ventricular fibrillation. Improvements in the therapy will require knowledge of how electric shocks interact with the myocardium to change cardiac transmembrane voltages. An """"""""activating function"""""""" is hypothesized to govern this interaction. This grant will test the hypothesis by 1) developing a method to optically mark hearts that will indicate the locations from which transmembrane voltages were recorded, 2) determining the relationships of the first and second spatial derivatives of the cardiac extracellular voltages induced by electric shocks to the changes in transmembrane voltages, 3) determining the relationships of myocardial structural inhomogeneities to the changes in transmembrane voltages produced by electric shocks, and 4) determining whether cell-to-cell uncoupling by ischemia, often present during defibrillation, alters the changes in transmembrane voltages produced by electric shocks. Transmembrane voltage changes in rabbit hearts will be measured with laser-scanner mapping of transmembrane voltage-sensitive dye fluorescence. To determine relationships between myocardial structure and transmembrane voltage changes, we will optically mark recording locations with the laser beam. Spatial derivatives of shock extracellular voltages will be produced in one and two dimensions with transparent indium tin oxide (ITO) and metallic shocking electrodes. The derivatives will be measured with metallic and ITO recording electrodes. Mapping of intracellular 6-carboxyfluorescein fluorescence recovery after photobleaching (FRAP) will indicate roles of intracellular diffusion that corresponds to the myocardial multicellular structure in the relationships that govern transmembrane voltage changes. FRAP will also indicate changes in diffusion constants introduced by cell-to-cell uncoupling during ischemia. Whether the uncoupling impacts on transmembrane voltage changes produced by shocks will be determined for global ischemia and for borders of ischemic regions. Thus, major factors responsible for transmembrane voltage changes during defibrillation in normal and ischemic hearts will be determined. This knowledge will help to optimize electrical therapy for life-threatening arrhythmias.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL052003-05
Application #
2854238
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1995-07-01
Project End
2003-05-31
Budget Start
1999-06-01
Budget End
2000-06-30
Support Year
5
Fiscal Year
1999
Total Cost
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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Sims, Jared A; Knisley Ast, Stephen B (2009) Epicardial conductors can lower the defibrillation threshold in rabbit hearts. IEEE Trans Biomed Eng 56:1196-9
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Dumas 3rd, John H; Knisley, Stephen B; Kinisley, Stephen B (2005) Two-photon excitation of di-4-ANEPPS for optical recording of action potentials in rabbit heart. Ann Biomed Eng 33:1802-7
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Knisley, Stephen B; Neuman, Michael R (2003) Simultaneous electrical and optical mapping in rabbit hearts. Ann Biomed Eng 31:32-41
Ramshesh, Venkat K; Knisley, Stephen B (2003) Spatial localization of cardiac optical mapping with multiphoton excitation. J Biomed Opt 8:253-9
Pollard, Andrew E; Cascio, Wayne E; Fast, Vladimir G et al. (2002) Modulation of triggered activity by uncoupling in the ischemic border. A model study with phase 1b-like conditions. Cardiovasc Res 56:381-92

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