Long term objectives of this project are to carry out basic research directed at improving understanding of cardiac electrophysiology in normal and perturbed cardiac states, to further develop and evaluate techniques for assessing cardiac electrophysiology from extracellular potential fields, and to facilitate transfer of measurement methods successfully used in experimental studies to the clinical arena. Studies proposed in this application represent extensions of as well as new directions for research accomplished during the current grant period. Acute experimental studies using canine hearts and electrocardiographic mapping techniques are proposed in five interrelated projects, each of which has multiple aims and hypotheses.
Specific aims address 1) fundamental study of between-beat (spatial) disparity of cycle length, its extent and potential role in arrhythmogenesis, 2) measurement, study and analysis of the interaction between and dynamics of cycle length inhomogeneity, activation sequence and repolarization disparity, 3) development and evaluation of a new method for directly and locally measuring electrophysiological parameters using patches of electrograms (PEGs) which integrate local spatial and temporal information and will attempt to dissect electrical components of propagating depolarization and repolarization waves, 4) assessment and analysis of the extent and characteristics of electrocardiographic information transfer from heart to body surfaces, particular as they relate to improving noninvasive, clinical methodology, and 5) development and evaluation of new techniques for use in pace mapping to facilitate and improve performance in EP lab procedures by reducing uncertainty, risk, and cost. Whereas emphasis of the preceding work focused on improving methodology for assessing cardiac behavior, the present application is directed toward identifying and assessing electrophysiological changes, particularly as they relate to abnormal or arrhythmogenic states. From a scientific perspective, rationale for the work is the benefit to be gained in terms of improved understanding of normal and abnormal cardiac behavior. From the perspective of health relatedness, the significance of the proposed work lies in benefit to be derived from improved capability to detect and a assess cardiac disease as well as to monitor therapeutic interventions in patients at risk.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cardiovascular and Pulmonary Research A Study Section (CVA)
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University of Utah
Internal Medicine/Medicine
Schools of Medicine
Salt Lake City
United States
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Fuller, M S; Sandor, G; Punske, B et al. (2000) Estimates of repolarization dispersion from electrocardiographic measurements. Circulation 102:685-91
Abildskov, J A; Lux, R L (2000) Simulated torsade de pointes--the role of conduction defects and mechanism of QRS rotation. J Electrocardiol 33:55-64
Lux, R L; Fuller, M S; MacLeod, R S et al. (1999) Noninvasive indices of repolarization and its dispersion. J Electrocardiol 32 Suppl:153-7
Ni, Q; MacLeod, R S; Lux, R L (1999) Three-dimensional activation mapping in ventricular muscle: interpolation and approximation of activation times. Ann Biomed Eng 27:617-26
Lux, R L; Fuller, M S; MacLeod, R S et al. (1998) QT interval dispersion: dispersion of ventricular repolarization or dispersion of QT interval? J Electrocardiol 30 Suppl:176-80
Abildskov, J A; Lux, R L (1997) Effects of heart rate on vulnerability to fibrillation in a computer model. J Electrocardiol 30:307-13
Abildskov, J A; Lux, R L (1997) Mechanisms in adrenergic dependent onset of torsades de pointes. Pacing Clin Electrophysiol 20:88-94
Green, L S; Fuller, M P; Lux, R L (1997) Three-dimensional distribution of ST-T wave alternans during acute ischemia. J Cardiovasc Electrophysiol 8:1413-9
Abildskov, J A; Lux, R L (1996) Effects of premature responses on vulnerability to fibrillation in a computer model. J Electrocardiol 29:213-21
Green, L S; Lux, R L; Ershler, P R et al. (1994) Resolution of pace mapping stimulus site separation using body surface potentials. Circulation 90:462-8

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