Electrical stimulation of the heart is commonplace in the treatment of cardiac arrhythmias. Implantable cardioverter/defibrillators is now a $1 billion industry in the U.S., with approximately 170,000 shocks delivered in people per year. Yet the fundamental mechanisms by which electrical fields interact with myocardial cells are still largely unknown. In the first (previous) three years of this project, the applicant has experimentally verified new theories for the electrical excitation of cardiac muscle in the vicinity of the stimulating electrodes, using optical measurements of cellular transmembrane potentials, and is working to test a theoretical model of field excitation of single cardiac cells. Nevertheless, the detailed biophysical mechanisms of interaction between electric fields and tissues in regions far from the electrodes are still largely unknown. Theories regarding possible facets of the excitatory process are quite advanced, and suggest that the tissue architecture may be the key player in determining the tissue response. However, at the present time experimental validation is still lacking. The central theme of this continuing five year application is the experimental investigation of the role of tissue architecture in the electrical excitation of cardiac muscle by applied electrical fields. The focus of attention in this project will shift away from amphibian heart, as studied in previous years, towards mamalian heart. The applicant proposes to utilize microlithographic technology to design patterned substrates of any shape on which cultured neonatal rat heart cells will be grown as cell strands. Using this approach, the applicant can then investigate tissue architectures of any desired topology. Features to be investigated include resistive discontinuities between cells, nonuniformities in electric field, strand boundaries, strand angle, strand curvature, strand branching, and changes in strand cross-sectional area. Voltage-sensitive dyes will be used to record the spatial patterns of transmembrane potential response to electric fields under each of these various conditions. Computer modeling will allow quantitative comparisons between experiment and current-day theoretical concepts. In this manner, the applicant will attempt to develop a comprehensive theoretical description of the influence to tissue architecture on the cellular membrane response to stimulating electric fields, component by component, so that the response of realistic tissue architectures can be better analyzed, understood, and ultimately, predicted.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Biomedical Engineering
Schools of Medicine
United States
Zip Code
Sharma, Vinod; Tung, Leslie (2004) Ionic currents involved in shock-induced nonlinear changes in transmembrane potential responses of single cardiac cells. Pflugers Arch 449:248-56
Entcheva, Emilia; Kostov, Yordan; Tchernev, Elko et al. (2004) Fluorescence imaging of electrical activity in cardiac cells using an all-solid-state system. IEEE Trans Biomed Eng 51:333-41
Iravanian, Shahriar; Nabutovsky, Yelena; Kong, Chae-Ryon et al. (2003) Functional reentry in cultured monolayers of neonatal rat cardiac cells. Am J Physiol Heart Circ Physiol 285:H449-56
Sharma, Vinod; Tung, Leslie (2002) Effects of uniform electric fields on intracellular calcium transients in single cardiac cells. Am J Physiol Heart Circ Physiol 282:H72-9
Sharma, Vinod; Lu, Steven N; Tung, Leslie (2002) Decomposition of field-induced transmembrane potential responses of single cardiac cells. IEEE Trans Biomed Eng 49:1031-7
Sharma, Vinod; Tung, Leslie (2002) Spatial heterogeneity of transmembrane potential responses of single guinea-pig cardiac cells during electric field stimulation. J Physiol 542:477-92
Iravanian, Shahriar; Tung, Leslie (2002) A novel algorithm for cardiac biosignal filtering based on filtered residue method. IEEE Trans Biomed Eng 49:1310-7
Sharma, V; Tung, L (2001) Theoretical and experimental study of sawtooth effect in isolated cardiac cell-pairs. J Cardiovasc Electrophysiol 12:1164-73
Tung, L; Kleber, A G (2000) Virtual sources associated with linear and curved strands of cardiac cells. Am J Physiol Heart Circ Physiol 279:H1579-90
Entcheva, E; Lu, S N; Troppman, R H et al. (2000) Contact fluorescence imaging of reentry in monolayers of cultured neonatal rat ventricular myocytes. J Cardiovasc Electrophysiol 11:665-76

Showing the most recent 10 out of 17 publications