Ventricular tachyarrhythmias result in 400,000 deaths annually in the U.S. The mechanisms and pathways involved in such arrhythmias have not been totally clarified and this has hampered therapy. The applicant has developed a technique, """"""""vector mapping"""""""", which can accurately determine the direction of myocardial impulse spread by summing orthogonally recorded bipolar electrograms. Experiments proposed in the first portion of this application will further refine this new methodology. This technique in combination with isochronal mapping will then be used to characterize conduction and identify reentry in experimental and clinical myocardial infarction. Project 1 will deal with the further technical development of the vector mapping technique; specifically examining instantaneous vectors. This will lay the ground work for future experiments utilizing vector mapping. Project 2 will examine the advantages of combining vector mapping with standard isochronal techniques in localizing sites of origin of ventricular tachycardia. This may demonstrate that vector mapping improves the speed and accuracy of tachycardia mapping and lead to its widespread clinical use in probe mapping of ventricular tachycardia during arrhythmia surgery. In Project 3, the ability of vector mapping to identify patterns of local conduction will be used in combination with standard techniques to examine uniform and non-uniform anisotropy related to fiber orientation in experimental myocardial infarction and normal human epicardium. These studies should increase the understanding of the details of impulse conduction in abnormal cardiac muscle and show how such conduction may be related to the development of arrhythmias. In Project 4, vector and isochronal mapping will be employed in an attempt to identify the anatomic pathways of reentrant circuits in ventricular myocardium. It is hoped that in addition of improving the speed, accuracy and availability of clinical mapping of ventricular tachycardia, the studies in this grant will improve the understanding of the pathways and mechanisms involved in reentrant arrhythmias and lead to the better direction of arrhythmia surgery and selection of alternative therapeutic approaches.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
First Independent Research Support & Transition (FIRST) Awards (R29)
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Cardiovascular and Pulmonary Research A Study Section (CVA)
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Northwestern University at Chicago
Schools of Medicine
United States
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Gordon, David; Kadish, Alan H; Koolish, Daniel et al. (2010) High-resolution electrical mapping of depolarization and repolarization alternans in an ischemic dog model. Am J Physiol Heart Circ Physiol 298:H352-9
Morady, F; Kadish, A H; Toivonen, L K et al. (1988) The maximum effect of an increase in rate on human ventricular refractoriness. Pacing Clin Electrophysiol 11:2223-34
Levine, J H; Moore, E N; Kadish, A H et al. (1988) Mechanisms of depressed conduction from long-term amiodarone therapy in canine myocardium. Circulation 78:684-91