It is not known which factors are responsible for maintaining ventricular fibrillation (VF): functional factors such as the nonuniform dispersion of refractoriness, action potential dispersion (APD) restitution, conduction velocity (CV) restitution, calcium cycling, and cardiac memory and anatomic factors such as coronary blood vessels, papillary muscles, Purkinje fibers, and myofiber orientation. The roles of these factors may differ (1) during different temporal stages of VF, (2) in different species, (3) with heart disease, and (4) in the presence of pharmacological agents. The goal of this competing renewal application is to answer important questions about which of these factors are most important in maintaining different types of VF. The proposed experiments use intramural and epicardial electrical recordings, a floating microelectrode recording, and, newly developed in our laboratory, intramural optical recordings in pigs and dogs to accomplish 4 specific aims.
Specific Aim 1 : Ascertain the determinants of APD variability and conduction block during VF.
Specific Aim 2 : Ascertain the role of Purkinje fibers in maintaining VF.
Specific Aim 3 : Ascertain the role of coronary vessels in causing block and reentry during VF.
Specific Aim 4 : Ascertain the role of papillary muscles in causing block and reentry during VF. Accomplishment of these specific aims will furnish the building blocks required to synthesize a global understanding of the complex, multifaceted question of how VF is maintained and how these factors are altered in different cardiac regions, during different temporal stages of VF, in different species, and in the presence of cardiac disease or pharmacologic agents. This understanding will give us new information needed to develop therapies to counteract these mechanisms of VF maintenance to prevent sudden cardiac arrest, one of the leading health problems in the world today.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL028429-26
Application #
7324752
Study Section
Electrical Signaling, Ion Transport, and Arrhythmias Study Section (ESTA)
Program Officer
Lathrop, David A
Project Start
1981-09-30
Project End
2009-11-30
Budget Start
2007-12-01
Budget End
2008-11-30
Support Year
26
Fiscal Year
2008
Total Cost
$353,201
Indirect Cost
Name
University of Alabama Birmingham
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Jin, Qi; Wu, Liqun; Dosdall, Derek J et al. (2018) Effects of combination of sotalol and verapamil on initiation, maintenance, and termination of ventricular fibrillation in swine hearts. Cardiovasc Ther 36:e12326
Jin, Qi; Dosdall, Derek J; Li, Li et al. (2014) Verapamil reduces incidence of reentry during ventricular fibrillation in pigs. Am J Physiol Heart Circ Physiol 307:H1361-9
Cheng, Kang-An; Dosdall, Derek J; Li, Li et al. (2012) Evolution of activation patterns during long-duration ventricular fibrillation in pigs. Am J Physiol Heart Circ Physiol 302:H992-H1002
Robichaux, Robert P; Dosdall, Derek J; Osorio, Jose et al. (2010) Periods of highly synchronous, non-reentrant endocardial activation cycles occur during long-duration ventricular fibrillation. J Cardiovasc Electrophysiol 21:1266-73
Dosdall, Derek J; Osorio, Jose; Robichaux, Robert P et al. (2010) Purkinje activation precedes myocardial activation following defibrillation after long-duration ventricular fibrillation. Heart Rhythm 7:405-12
Li, Li; Jin, Qi; Dosdall, Derek J et al. (2010) Activation becomes highly organized during long-duration ventricular fibrillation in canine hearts. Am J Physiol Heart Circ Physiol 298:H2046-53
Kong, Wei; Ideker, Raymond E; Fast, Vladimir G (2009) Transmural optical measurements of Vm dynamics during long-duration ventricular fibrillation in canine hearts. Heart Rhythm 6:796-802
Ideker, Raymond E; Rogers, Jack M; Fast, Vladimir et al. (2009) Can mapping differentiate microreentry from a focus in the ventricle? Heart Rhythm 6:1666-9
Tabereaux, Paul B; Dosdall, Derek J; Ideker, Raymond E (2009) Mechanisms of VF maintenance: wandering wavelets, mother rotors, or foci. Heart Rhythm 6:405-15
Ideker, Raymond E; Kong, Wei; Pogwizd, Steven (2009) Purkinje fibers and arrhythmias. Pacing Clin Electrophysiol 32:283-5

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