Application) The long-term objective of this renewal project is to understand, at a more cellular/subcellular level, the electrical abnormalities defined in myocytes cellular/subcellular level, the electrical abnormalities defined in myocytes that have survived in the epicardial border zone of the infarcted heart 5 days, 14 days and 2 months post coronary artery occlusion. These abnormalities contribute to the occurrence of life threatening ventricular arrhythmias post myocardial infarction.
The specific aims are as follows: 1) to determine the function of specific ionic currents in cells dispersed from the central common pathway versus the peripheral tissues of mapped reentrant the central common pathway versus the peripheral tissues of mapped reentrant circuits of the epicardial border zone of the 5 day infarcted heart, 2) to determine the function of specific ion currents of cells dispersed from the border zone of the 14 day and 2 month infarcted heart, 3) to determine what changes in the cardiac sodium channel at the level of the single channel underlie the observed reduced amplitude and altered kinetics of the Na current in 5 day border zone cells, 4) to determine the role of altered tyrosine kinase function in altered Ca2+ and K+ currents and their pharmacology in 5 day border zone cells, and 5) to determine the function and pharmacology of delayed rectified K+ currents in border zone cells in particular to identify Kvl1.5 channel proteins. Studies will be completed using whole cell and cell border zone of hearts post coronary artery occlusion. The results of these studies will provide a more detailed understanding of the ionic basis of electrical remodeling in cells surviving in the healing and healed hearts post infarction and in so doing will help identify new molecular targets for treatment of reentrant ventricular arrhythmias that occur during these times.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL030557-16
Application #
6336625
Study Section
Project Start
2000-08-01
Project End
2001-07-31
Budget Start
Budget End
Support Year
16
Fiscal Year
2000
Total Cost
$225,543
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Ciaccio, Edward J; Chow, Anthony W; Kaba, Riyaz A et al. (2008) Detection of the diastolic pathway, circuit morphology, and inducibility of human postinfarction ventricular tachycardia from mapping in sinus rhythm. Heart Rhythm 5:981-91
Ciaccio, Edward J; Ashikaga, Hiroshi; Kaba, Riyaz A et al. (2007) Model of reentrant ventricular tachycardia based on infarct border zone geometry predicts reentrant circuit features as determined by activation mapping. Heart Rhythm 4:1034-45
Ciaccio, Edward J; Micheli-Tzanakou, Evangelia (2007) Development of gradient descent adaptive algorithms to remove common mode artifact for improvement of cardiovascular signal quality. Ann Biomed Eng 35:1146-55
Cabo, Candido; Boyden, Penelope A (2006) Heterogeneous gap junction remodeling stabilizes reentrant circuits in the epicardial border zone of the healing canine infarct: a computational study. Am J Physiol Heart Circ Physiol 291:H2606-16
Cabo, Candido; Yao, Jianan; Boyden, Penelope A et al. (2006) Heterogeneous gap junction remodeling in reentrant circuits in the epicardial border zone of the healing canine infarct. Cardiovasc Res 72:241-9
Terrenoire, Cecile; Clancy, Colleen E; Cormier, Joseph W et al. (2005) Autonomic control of cardiac action potentials: role of potassium channel kinetics in response to sympathetic stimulation. Circ Res 96:e25-34
Fishman, Glenn I (2005) Gap junction remodeling and ventricular arrhythmias. Heart Rhythm 2:887-9
Ciaccio, Edward J; Saltman, Adam E; Hernandez, Oscar M et al. (2005) Multichannel data acquisition system for mapping the electrical activity of the heart. Pacing Clin Electrophysiol 28:826-38
Baba, Shigeo; Dun, Wen; Cabo, Candido et al. (2005) Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia. Circulation 112:2386-96
Ciaccio, Edward J (2005) Ventricular tachycardia duration and form are associated with electrical discontinuities bounding the core of the reentrant circuit. J Cardiovasc Electrophysiol 16:646-54

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