Our goal is to improve understanding of the mechanisms for cardiac arrhythmias, the ways in which these mechanisms can be precisely identified and the mechanisms of action of antiarrhythmic drugs to permit more accurate diagnosis and more effective treatment. We have selected this area because cardiac arrhythmias such as vent- ricular tachycardia and fibrillation are the major cause of death in individuals with coronary artery disease or heart failure.
Our specific aims are to determine the mechanisms by which ischemia and infarction bring about alterations in the electrical activity of cardiac cells that lead to reentrant rhythms, how both the functional and structural properties of the circus path influence reentrant rhythms and their responses to drugs and which actions of antiarrhythmic drugs are necessary for prevention and termina- tion of reentrant excitation. We will attempt to answer these questions by closely integrated studies examining the effects of ischemic factors and antiarrhythmic drugs on single channel currents studied with patch-clamp methods in single myocytes or whole-cell currents studied with voltage-clamp and intracellular dialysis in both normal myocardial and Purkinje cells and those modified by acute and subacute infarction, by studies using ion selective microelectrodes to measure alterations in intracellular and extracellular composition caused by factors designed to mimic ischemia, by studies with microelectrodes on normal cardiac tissues and tissues damaged by ischemia and by studies on reentrant arrhythmias and drug actions in canine models of reentrant arrhythmias. These models include two types of reentrant atrial arrhythmias and also ventricular tachycardia in the infarcted heart. Finally, we will use a new optical recording method to study ventricular tachycardia and ventricular fibrillation and determine how electrical shocks terminate reentry and fibrillatory rhythms.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL030557-10
Application #
2216648
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1984-01-01
Project End
1994-12-31
Budget Start
1993-01-01
Budget End
1994-12-31
Support Year
10
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Pharmacology
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
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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