The goal of this proposal is to answer important questions about reentry during ventricular fibrillation (VF) that are crucial for improving therapy for sudden cardiac arrest: How is reentry maintained? How are these mechanisms altered by disease or drugs? Can reentry during VF be prevented or halted by pacing.
Specific Aim 1 : Use electrical mapping to determine if a mother rotor exists in swine. In small hearts a stable, stationary reentrant circuit, called the mother rotor, has been reported in the fastest activating region during VF, called the dominant domain. These findings may not be true in larger hearts. We will perform electrical mapping studies in the larger hearts of pigs to test the hypotheses that (1) a mother rotor is located at the insertion of the posterior LV papillary muscle and (2) the stability of this reentry is affected by drugs and myocardialinfarction.
Specific Aim 2 : Use electrical and optical mapping to optimize pacing techniques to halt or prevent VF. We will use mapping to optimize stimulation waveforms and electrodes which will be used to test the hypotheses that pacing in or near the dominant domain (1) will capture the largest volume of myocardium, (2) can halt reentry and VF, and (3) can prevent VF if performed during the first cycles of an arrhythmia before reentry has developed.
Specific Aim 3 : Use electrical mapping and monophasic action potential (MAP) recordings to investigate the mechanisms of VF maintenance in humans. We will perform electrical epicardial mapping and epicardial MAP recordings during VF in patients undergoing cardiac surgery and will record from basket electrodes in patients in the clinical electrophysiology laboratory to test the hypotheses that (1) there is a single dominant domain with a VF activation rate faster than in the remainder of the ventricles, (2) conduction block occurs more frequently along the paths of coronary vessels or in regions with a high spatial dispersion of refractoriness, and (3) cardiac disease and drugs alter the organization of VF.
Specific Aim 4 : Use electrical and MAP recordings to determine if it is possible to capture a portion of the myocardium by pacing during VF in humans. We will test the hypotheses that pacing from the dominant domain (1) captures the maximum amount of tissue during VF and (2) halts the most organized types of VF.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL066256-09
Application #
7788186
Study Section
Electrical Signaling, Ion Transport, and Arrhythmias Study Section (ESTA)
Program Officer
Lathrop, David A
Project Start
2001-02-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2012-03-31
Support Year
9
Fiscal Year
2010
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; 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
Osorio, Jose; Dosdall, Derek J; Tabereaux, Paul B et al. (2012) Effect of chest compressions on ventricular activation. Am J Cardiol 109:670-4
Jennings, John M; Ideker, Raymond E (2010) Why do thrombi form in the left but not the right atrium in atrial fibrillation: differences in platelet P-selectin levels? Heart Rhythm 7:1184-5
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
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
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
Robertson, Peter G; Huang, Jian; Chen, Kang A et al. (2009) Increased cycle length during long-duration ventricular fibrillation is caused by decreased upstroke velocity as well as prolonged refractoriness. Heart Rhythm 6:378-84

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