Pathologic conditions in which electrical remodeling occurs and which are prone to ventricular and atrial arrhythmias are frequently associated with structural remodeling, such as fibrosis and hypertrophy. The presence of structural heart disease is the number one risk factor for sudden cardiac death due to ventricular arrhythmias. Most patients with structural disease prone to arrhythmias have hypertrophy and conditions with fibrosis, such as heart failure and ischemia. Similar, atrial fibrillation is associated with atrial hypertrophy and fibrosis both clinically and in several animal models. However, how this structural remodeling effects electrical remodeling or whether they are simply epiphenomenon is unknown. Since hypertrophy and fibrosis occur coincidentally in most pathologic conditions, the electrophysiologic effect of either alone, has not been well studied. Interventions aimed at blocking this pathologic structural remodeling may prevent electrical remodeling, ultimately rendering the heart resistant to fibrillation. We have recently identified several gene products which, when expressed in the myocardium of transgenic mice, block adverse structural remodeling. In particular two gene products we will study prevent the development of fibrosis and hypertrophy, respectively. We propose that the favorable effect of these gene products on structural remodeling will prevent electrical remodeling and serve to block the generation of a pro- arrhythmogenic substrate. We will test this hypothesis directly in the ventricles and atria of transgenic animals.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL066362-02
Application #
6391220
Study Section
Special Emphasis Panel (ZHL1-CSR-O (S1))
Program Officer
Lathrop, David A
Project Start
2000-09-30
Project End
2004-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
2
Fiscal Year
2001
Total Cost
$369,191
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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