The development of advanced technologies for electrophysiological mapping of cardiac propagation has been a defining factor in recent successes both in basic understanding of arrhythmia mechanisms and clinical applications such as mapping-guided radiofrequency ablation. However, one of the major challenges both in basic and clinical cardiac electrophysiology remains the mapping of abnormally conducting arrhythmogenic regions hidden inside the myocardial wall. The ultimate goal of this proposal is to develop a minimally invasive 3D tomographic optical mapping technique utilizing novel near-infrared (NIR) voltage-sensitive dyes, which will significantly enhance one's ability to study electrical excitation inside the myocardial wall. During the previous period of support, we have conducted extensive modeling and experimental studies that indicate the feasibility of our method. The next step will be to implement, validate, and assess the potential of the new technique for 3D mapping of normal myocardium and physiologically relevant arrhythmogenic ischemic substrates.
The Specific Aims of this proposal are: 1) Build a fast optical tomographic system for the time-resolved 3D imaging of intra-mural electrical waves in isolated coronary-perfused ventricular wall preparations. 2) Perform the 3D reconstructions of intramural electrical excitation wave in Tyrode-perfused and blood-perfused pig ventricular wall preparations. 3) Test the accuracy of the reconstructions under conditions simulating non- uniform staining patterns characteristic of arrhythmogenic substrates (ischemic border, infarction scar). 4) Utilize the new techniques to determine the role of 3D geometry of perfusion territories in arrhythmogenesis during acute regional ischemia. We will test the hypothesis that the anatomy of the perfusion territory of a given coronary artery defines the geometry of the ischemic region and is a major factor that determines the pattern of electrical propagation emerging after occlusion of that artery. Successful completion of the proposed Specific Aims will produce, validate, and test both under normal and clinically relevant conditions a fast new tomographic method for the 3D optical imaging of intra-myocardial excitation. It will also provide new mechanistic information regarding the links between the anatomy of perfusion territories and ischemia-related conduction abnormalities.

Public Health Relevance

The goal of the proposed studies is to develop an optical imaging technology for detecting sources of arrhythmia hidden deep inside the myocardial wall. Such sources emerge during the blockage of arteries feeding cardiac muscle and often cause sudden cardiac death. The new technology will help to understand the mechanisms of initiation of such sources, which is the key to developing effective anti-arrhythmic therapies and prevention of sudden cardiac death.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL071762-08
Application #
8098007
Study Section
Electrical Signaling, Ion Transport, and Arrhythmias Study Section (ESTA)
Program Officer
Lathrop, David A
Project Start
2002-12-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
8
Fiscal Year
2011
Total Cost
$274,750
Indirect Cost
Name
Upstate Medical University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
Caldwell, Bryan J; Trew, Mark L; Pertsov, Arkady M (2015) Cardiac response to low-energy field pacing challenges the standard theory of defibrillation. Circ Arrhythm Electrophysiol 8:685-93
Kanaporis, Giedrius; Martisiene, Irma; Jurevicius, Jonas et al. (2012) Optical mapping at increased illumination intensities. J Biomed Opt 17:96007-1
Mitrea, Bogdan G; Caldwell, Bryan J; Pertsov, Arkady M (2011) Imaging electrical excitation inside the myocardial wall. Biomed Opt Express 2:620-33
Caldwell, Bryan J; Wellner, Marcel; Mitrea, Bogdan G et al. (2010) Probing field-induced tissue polarization using transillumination fluorescent imaging. Biophys J 99:2058-66
Walton, Richard D; Mitrea, Bogdan G; Pertsov, Arkady M et al. (2009) A novel near-infrared voltage-sensitive dye reveals the action potential wavefront orientation at increased depths of cardiac tissue. Conf Proc IEEE Eng Med Biol Soc 2009:4523-6
Matiukas, Arvydas; Pertsov, Arkady M; Kothari, P et al. (2009) Optical mapping of electrical heterogeneities in the heart during global ischemia. Conf Proc IEEE Eng Med Biol Soc 2009:6321-4
Mitrea, Bogdan G; Wellner, Marcel; Pertsov, Arkady M (2009) Monitoring intramyocardial reentry using alternating transillumination. Conf Proc IEEE Eng Med Biol Soc 2009:4194-7
Zemlin, Christian W; Mitrea, Bogdan G; Pertsov, Arkady M (2009) Spontaneous onset of atrial fibrillation. Physica D 238:969-975
Danko, Charles G; Pertsov, Arkady M (2009) Identification of gene co-regulatory modules and associated cis-elements involved in degenerative heart disease. BMC Med Genomics 2:31
Zemlin, Christian W; Bernus, Olivier; Matiukas, Arvydas et al. (2008) Extracting intramural wavefront orientation from optical upstroke shapes in whole hearts. Biophys J 95:942-50

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