Sudden cardiac death is the leading cause of fatalities in the industrialized world. Ventricular fibrillation (VF) is the underlying cause of the majority of these deaths. The only effective means to save the lives of these individuals is to apply high energy electric fields from widely spaced electrodes to terminate VF. These high energy """"""""shocks"""""""" can also induce VF, if they are applied during the """"""""vulnerable period"""""""" of normal sinus or pace rhythms. The outcome following a shock is determined largely by the charges in transmembrane potential (Vm) during the shock. However, very little is known about the shock- induced changes in Vm in the whole heart and how they relate to the events following a shock. It is thought that the changes in Vm during applied electric fields is a nonlinear function of: 1) the Vm pattern immediately before the sock; 2) the strength and time course (waveform) of the electric field; and 3) the dynamic response of cardiac cells to stimuli. We hypothesize that: I Electric fields greater than some critical strength prevent wave front propagation throughout the heart, and if these shocks are sufficiently long in duration, a steady state pattern of Vm will be established. Vm at the end of short duration shocks, for a constant electric field above this critical strength, can be predicted from Vm at the beginning of the shock and the steady state Vm pattern achieved during long duration shocks. II) The nonlinear response of cardiac cells, most importantly all-or-none depolarization and repolarization, plays an important role in the generation of new wave fronts at the end of the shock which may lead to reentry. III) The spatial pattern of Vm at the end of the shock can be related to reentry formation and hence the outcome resulting from the shock. In particular, spatial patterns of cardiac phase can be formally related to reentry via phase singularities and reentry will only occur following a shock if a phase singularity exists at the end of the shock. Our overall goal is to provide the first precise understanding of the factors that determine the changes in Vm during a shock and how the pattern of Vm at the end of the applied electric field affects the outcome of the shock. This goal will be achieved by: 1) recording Vm from the surface of the heart during and following electric shocks given during pacing, monomorphic tachycardia, and fibrillation; 2) recording them response to stimuli in isolated ventricular myocytes; and 3) relating the patterns of membrane potential at the end of shocks to outcome. Furthermore, changes in Vm in single cells and patterns of Vm from the heart surface will be analyzed in terms of a cardiac phase variable which provides a mathematical framework for the examination of cellular dynamics and reentrant waves.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL063267-02
Application #
6390475
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Lathrop, David A
Project Start
2000-04-01
Project End
2004-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
2
Fiscal Year
2001
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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Gray, Richard A; Chattipakorn, Nipon (2005) Termination of spiral waves during cardiac fibrillation via shock-induced phase resetting. Proc Natl Acad Sci U S A 102:4672-7
Chattipakorn, Nipon; Banville, Isabelle; Gray, Richard A et al. (2004) Effects of shock strengths on ventricular defibrillation failure. Cardiovasc Res 61:39-44
Evans, Frederick G; Gray, Richard A (2004) Shock-induced epicardial and endocardial virtual electrodes leading to ventricular fibrillation via reentry, graded responses, and transmural activation. J Cardiovasc Electrophysiol 15:79-87
Trayanova, Natalia A; Gray, Richard A; Bourn, David W et al. (2003) Virtual electrode-induced positive and negative graded responses: new insights into fibrillation induction and defibrillation. J Cardiovasc Electrophysiol 14:756-63
Chattipakorn, Nipon; Ideker, Raymond E (2003) The vortex at the apex of the left ventricle: a new twist to the story of the electrical induction of rotors? J Cardiovasc Electrophysiol 14:303-5
Gray, R A; Mornev, O A; Jalife, J et al. (2001) Standing excitation waves in the heart induced by strong alternating electric fields. Phys Rev Lett 87:168104

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