This is a renewal request for a Program Project Grant focusing on cardiac electrophysiology and cardiac contractility with the goal of developing new and useful insight, diagnostic methods, and treatment of cardiac disease. To this end, the work is conducted by a tightly-knit group of investigators from varied disciplines including physicians, physiologists, engineers, physicists, and computer scientists. The central theme of the program is to determine the functional role of anatomical complexities in the electrical and mechanical behavior of the heart. Recent work in this program led to the hypothesis that propagation in cardiac muscle is discontinuous due to recurrent discontinuities of intracellular resistivity that affect the membrane currents. Based on this finding, work is proposed to develop new theory and information about propagation in cardiac muscle. New biophysical models have been developed that allow detailed electrical measurements of propagation and repolarization in anisotropic muscle, as well as of total heart electrical activity. With these methods our objective is to develop conceptual and mathematical models which will provide new information about the origin and prepetuation of arrhythmias, the use of extracellular (rather than intracellular) potentials for detailed study of propagation abnormalities, and to understand the origin of body surface potentials on a quantitative basis. The ultimate goal of the cardiac muscle mechanic studies is to obtain a complete description of th changes in cardiac contractility in normal and abnormal states, and to understand their origin at the sarcomere level.
This aim will be pursued through in vitro studies of the dynamic properties of sarcomere shortening to estimate the time-course and kinetics of cross-bridge formation and dissociation in trabeeculae and by study of contractility in single cardiac cells. Only through such studies, where sarcomere length and loading are known, can the basic mechanical properties of the heart be determined.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL011307-21
Application #
3097443
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1977-05-01
Project End
1992-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
21
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Wu, J; Johnson, E A; Kootsey, J M (1996) A quasi-one-dimensional theory for anisotropic propagation of excitation in cardiac muscle. Biophys J 71:2427-39
Dolber, P C; Bauman, R P; Rembert, J C et al. (1994) Regional changes in myocyte structure in model of canine right atrial hypertrophy. Am J Physiol 267:H1279-87
Ihara, T; Barr, R C (1994) Electrocardiographic inverse solution for ectopic origin of excitation in two-dimensional propagation model. Med Biol Eng Comput 32:S41-50
Dolber, P C; Spach, M S (1993) Conventional and confocal fluorescence microscopy of collagen fibers in the heart. J Histochem Cytochem 41:465-9
Cabo, C; Barr, R C (1992) Reflection after delayed excitation in a computer model of a single fiber. Circ Res 71:260-70
Johnson, E A; Lemieux, D R; Kootsey, J M (1992) Sodium-calcium exchange: derivation of a state diagram and rate constants from experimental data. J Theor Biol 156:443-83
Barr, R C; Plonsey, R (1992) Electrophysiological interaction through the interstitial space between adjacent unmyelinated parallel fibers. Biophys J 61:1164-75
Nesterenko, V V; Lastra, A A; Rosenshtraukh, L V et al. (1992) A proarrhythmic response to sodium channel blockade: modulation of the vulnerable period in guinea pig ventricular myocardium. J Cardiovasc Pharmacol 19:810-20
Dolber, P C; Beyer, E C; Junker, J L et al. (1992) Distribution of gap junctions in dog and rat ventricle studied with a double-label technique. J Mol Cell Cardiol 24:1443-57
Cabo, C; Barr, R C (1992) Propagation model using the DiFrancesco-Noble equations. Comparison to reported experimental results. Med Biol Eng Comput 30:292-302

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