Atrial fibrillation (AF) is the most common arrhythmia in the U.S. Growing evidence suggests that the rapid rates during AF create changes which enhances the risk of AF itself. However, the mechanisms that lead from paroxysmal to chronic AF (""""""""electrical remodeling"""""""") are poorly understood. The proposed project attempts to determine the neural, ionic, electrophysiologic and structural mechanism of this self-perpetuating nature of (AF). The applicant plans to test the hypothesize that heterogeneous distribution of autonomic innervation and cellular connections on the atria are responsible for paroxysms of AF; and as the frequency of these paroxysms increase, chronic intracellular calcium overload occurs, resulting in permanent cell damage, leading to the downhill cascade towards chronic AF. At various stages during the transition from paroxysmal to chronic AF in a canine model we plan to 1) determine electrophysiologic measures of AF inducibility and organization; 2) map the distribution of parasympathetic and sympathetic innervation using autoradiography; 3) measure intracellular calcium using fluorescent dyes; 4) map the cellular connections (gap junctions) in the atria using immunohistochemistry; and 5) identify structural and cellular abnormalities in the atria.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003703-03
Application #
2771187
Study Section
Special Emphasis Panel (ZHL1-CSR-Y (M1))
Project Start
1996-09-01
Project End
2001-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
3
Fiscal Year
1998
Total Cost
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
Sih, H J; Zipes, D P; Berbari, E J et al. (2000) Differences in organization between acute and chronic atrial fibrillation in dogs. J Am Coll Cardiol 36:924-31
Jayachandran, J V; Sih, H J; Winkle, W et al. (2000) Atrial fibrillation produced by prolonged rapid atrial pacing is associated with heterogeneous changes in atrial sympathetic innervation. Circulation 101:1185-91
Jayachandran, J V; Zipes, D P; Weksler, J et al. (2000) Role of the Na(+)/H(+) exchanger in short-term atrial electrophysiological remodeling. Circulation 101:1861-6
Sih, H J (2000) Evidence of heterogeneous remodeling in canine atrial fibrillation. J Electrocardiol 33 Suppl:141-5
Sih, H J; Zipes, D P; Berbari, E J et al. (1999) A high-temporal resolution algorithm for quantifying organization during atrial fibrillation. IEEE Trans Biomed Eng 46:440-50
Olgin, J E; Sih, H J; Hanish, S et al. (1998) Heterogeneous atrial denervation creates substrate for sustained atrial fibrillation. Circulation 98:2608-14
Olgin, J E; Jayachandran, J V; Engesstein, E et al. (1998) Atrial macroreentry involving the myocardium of the coronary sinus: a unique mechanism for atypical flutter. J Cardiovasc Electrophysiol 9:1094-9