Abstract

This research will obtain fundamental knowledge of effects of electrical defibrillation shocks in the heart that is needed to understand defibrillation. Defibrillation is thought to occur in three steps: 1) The shock changes transmembrane voltages during the shock pulse. 2) The changes in transmembrane voltages alter transmembrane voltage-dependent ion channels which excite the cells or prolong action potential repolarization after the pulse. 3) The excitation or prolonged repolarization produces defibrillation. Mechanisms for the steps are not known. This project will use transmembrane voltage-sensitive dye fluorescence and a laser scanner system to study up to 127 locations on isolated arterially perfused rabbit hearts. The distributions of transmembrane voltages during the shock pulse, the excitation or prolonged repolarization after the pulse and the changes in activation patterns and block required to produce defibrillation will be determined. The maximum dV/dt of action potentials measured with microelectrodes and the sodium channel modulators, tetrodotoxin and high potassium, will be used to study transmembrane voltage-dependent fast inward sodium channel recovery during monophasic and biphasic shocks. The importance of the fast inward sodium channel recovery for the prolonged repolarization produced by the shocks will be determined. The impacts of pharmacological sodium, calcium or potassium channel blockade, present in some patients who receive shocks. on prolonged repolarization will be determined. Calcium-sensitive dye fluorescence will be measured with the laser scanner system to study the roles of ischemia, fibrillation and the transmembrane voltages during shocks in producing elevated intracellular calcium. The importance of the elevated intracellular calcium for spontaneous fibrillation induction, fibrillation maintenance and defibrillation will be determined. The project will yield insights that are necessary in order to advance understanding of cellular bases of defibrillation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL052003-07
Application #
6430832
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1995-07-01
Project End
2003-06-30
Budget Start
2000-08-16
Budget End
2001-06-30
Support Year
7
Fiscal Year
2000
Total Cost
$107,625
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Sims, Jared A; Pollard, Andrew E; White, Peter S et al. (2010) Stimulatory current at the edge of an inactive conductor in an electric field: role of nonlinear interfacial current-voltage relationship. IEEE Trans Biomed Eng 57:442-9
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
Ramshesh, Venkat K; Knisley, Stephen B (2006) Use of light absorbers to alter optical interrogation with epi-illumination and transillumination in three-dimensional cardiac models. J Biomed Opt 11:024019
Knisley, Stephen B; Pollard, Andrew E (2005) Use of translucent indium tin oxide to measure stimulatory effects of a passive conductor during field stimulation of rabbit hearts. Am J Physiol Heart Circ Physiol 289:H1137-46
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
Liau, Joy; Dumas, John; Janks, Deborah et al. (2004) Cardiac optical mapping under a translucent stimulation electrode. Ann Biomed Eng 32:1202-10
Kong, Wei; Walcott, Gregory P; Smith, William M et al. (2003) Emission ratiometry for simultaneous calcium and action potential measurements with coloaded dyes in rabbit hearts: reduction of motion and drift. J Cardiovasc Electrophysiol 14:76-82
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

Showing the most recent 10 out of 29 publications