The electrophysiological mechanisms of polymorphic ventricular tachycardia and fibrillation remain poorly understood. The surface manifestations as well as limited three-dimensional (3D) information obtained using arrhythmias. In the proposed study, we will utilize a new experimental method (transillumination) that should significantly enhance our ability to study 3D reentrant activity via visualization of its organizing center-filament. Using transillumination in combination with conventional optical mapping we will test the following major hypotheses: 1. In 3D ventricular myocardium, the filament tends to align parallel to myocardial fibers. 3. Sustained polymorphic ventricular tachycardia and fibrillation are maintained by stable filaments concealed in the depth of myocardial wall. Hypotheses 1 and 2 are based on preliminary computer simulations of 3D myocardial wall with realistic fiber geometry. Hypotheses 3 is supported by electrically induced tachycardia or fibrillation.
The specific aims of our study are as follows: 1. To identify the mechanisms controlling spatial orientation and dynamics of the filament in computer models of ventricular wall with realistic fiber organization. 2. To study the evolution of the scroll-wave filament during sustained and non-sustained arrhythmias in isolated coronary-perfused preparations of sheep right and left ventricles using a transillumination technique. 3. To determine the role of stable filaments in the maintenance in the maintenance mechanisms of complex reentrant ventricular arrhythmias. The ultimate goal of this study is to assess the possibility of terminating those arrhythmias by controlling the evolution of the scroll wave filament.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL039707-11
Application #
6312804
Study Section
Project Start
2000-05-01
Project End
2001-04-30
Budget Start
Budget End
Support Year
11
Fiscal Year
2000
Total Cost
$564,536
Indirect Cost
Name
Upstate Medical University
Department
Type
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
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Takemoto, Yoshio; Ramirez, Rafael J; Yokokawa, Miki et al. (2016) Galectin-3 Regulates Atrial Fibrillation Remodeling and Predicts Catheter Ablation Outcomes. JACC Basic Transl Sci 1:143-154
Filgueiras-Rama, David; Jalife, José (2016) STRUCTURAL AND FUNCTIONAL BASES OF CARDIAC FIBRILLATION. DIFFERENCES AND SIMILARITIES BETWEEN ATRIA AND VENTRICLES. JACC Clin Electrophysiol 2:1-3
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