Atrial fibrillation is the most common arrhythmia and accounts for significant morbidity and mortality. Recently, evidence has suggested that atrial fibrillation may be a result of focal activity from the atrial myocardium of the pulmonary veins. However, the mechanism of this form of atrial fibrillation is not known nor is the reason why there is a predominance of these foci in the pulmonary veins. It is the long-term goal of this application to study the electrophysiologic properties of the atrial myocardium of the pulmonary veins and define structure/function relationships of the arrhythmogenic substrate. In particular, we will utilize high resolution optical mapping of cardiac activation in a canine model of atrial dilatation and atrial fibrillation to identify the precise mechanism of focal atrial fibrillation. In the first Specific Aim, we will identify the potential substrate for arrhythmias in the myocardium of the pulmonary vein and identify the role of triggers such as calcium channel agonists and a-adrenergic agonists. In the second Specific Aim, we will study the role of acute pulmonary vein dilatation on the substrate and triggering of focal atrial fibrillation. In the third Specific Aim, we will study the effect chronic pulmonary vein dilatation on the substrate and mechanism of focal atrial fibrillation. In the last Specific Aim, we will study how focal discharges from the pulmonary vein myocardium interact with the vulnerable substrate of the remainder of the atrium to produce sustained atrial fibrillation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL072854-04
Application #
7109238
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Program Officer
Lathrop, David A
Project Start
2003-09-01
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2008-08-31
Support Year
4
Fiscal Year
2006
Total Cost
$369,849
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Nguyen, Duy T; Ding, Chunhua; Wilson, Emily et al. (2010) Pirfenidone mitigates left ventricular fibrosis and dysfunction after myocardial infarction and reduces arrhythmias. Heart Rhythm 7:1438-45
Everett 4th, Thomas H; Wilson, Emily E; Hulley, George S et al. (2010) Transmural characteristics of atrial fibrillation in canine models of structural and electrical atrial remodeling assessed by simultaneous epicardial and endocardial mapping. Heart Rhythm 7:506-17
Everett 4th, Thomas H; Lee, Ken W; Wilson, Emily E et al. (2009) Safety profiles and lesion size of different radiofrequency ablation technologies: a comparison of large tip, open and closed irrigation catheters. J Cardiovasc Electrophysiol 20:325-35
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Marcus, Gregory M; Whooley, Mary A; Glidden, David V et al. (2008) Interleukin-6 and atrial fibrillation in patients with coronary artery disease: data from the Heart and Soul Study. Am Heart J 155:303-9
Everett 4th, Thomas H; Olgin, Jeffrey E (2007) Atrial fibrosis and the mechanisms of atrial fibrillation. Heart Rhythm 4:S24-7
Everett 4th, Thomas H; Wilson, Emily E; Olgin, Jeffrey E (2007) Effects of atrial fibrillation substrate and spatiotemporal organization on atrial defibrillation thresholds. Heart Rhythm 4:1048-56

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