Ventricular repolarization properties are electrotonically modulated by ventricular activation sequence. In previous studies we found that local repolarization at a site was longer when activation was initiated at the site than when activation was initiated at a distance from it or when collision of activation fronts occurred near it. The studies we are proposing will determine the factors responsible for the magnitude of the modulation of repolarization properties by activation order, and the effects of activation sequence dependent changes in repolarization properties on inhomogeneity of those properties. Since inhomogeneity of repolarization properties is a factor in arrhythmia vulnerability we will study the effects of activation sequence induced inhomogeneity of repolarization properties on arrhythmia vulnerability. In addition to the relation to arrhythmias, collision of excitation fronts during both normal and abnormal ventricular excitation is likely to be one of the determinants of the distribution of local repolarization properties. Definition of these effects of collision would contribute to basic physiologic knowledge and is relevant to understanding the physiologic basis of ECG T waveform. Studies will include experiments using isolated superfused tissues, isolated perfused hearts, whole animals and computer simulations. The results will contribute to understanding the mechanism for the dependence of repolarization properties on activation sequence and have clinical implications with regard to ECG waveform and arrhythmia vulnerability.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL034288-01
Application #
3347055
Study Section
Cardiovascular Study Section (CVA)
Project Start
1985-09-01
Project End
1990-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Spitzer, K W; Sato, N; Tanaka, H et al. (1997) Electrotonic modulation of electrical activity in rabbit atrioventricular node myocytes. Am J Physiol 273:H767-76
Pollard, A E; Spitzer, K W; Burgess, M J (1997) Contributions of the specialized conduction system to the activation sequence in the canine pulmonary conus. Am J Physiol 273:H446-63
Levi, A J; Li, J; Spitzer, K W et al. (1996) Effect on the indo-1 transient of applying Ca2+ channel blocker for a single beat in voltage-clamped guinea-pig cardiac myocytes. J Physiol 494 ( Pt 3):653-73
Burgess, M J; Pollard, A E; Spitzer, K W et al. (1995) Effects of premature beats on repolarization of postextrasystolic beats. Circulation 92:1969-80
Levi, A J; Spitzer, K W; Kohmoto, O et al. (1994) Depolarization-induced Ca entry via Na-Ca exchange triggers SR release in guinea pig cardiac myocytes. Am J Physiol 266:H1422-33
Zubair, I; Pollard, A E; Spitzer, K W et al. (1994) Effects of activation sequence on the spatial distribution of repolarization properties. J Electrocardiol 27:115-27
Xu, P; Spitzer, K W (1994) Na-independent Cl(-)-HCO3- exchange mediates recovery of pHi from alkalosis in guinea pig ventricular myocytes. Am J Physiol 267:H85-91
Pollard, A E; Burgess, M J; Spitzer, K W (1993) Computer simulations of three-dimensional propagation in ventricular myocardium. Effects of intramural fiber rotation and inhomogeneous conductivity on epicardial activation. Circ Res 72:744-56
Pollard, A E; Hooke, N; Henriquez, C S (1992) Cardiac propagation simulation. Crit Rev Biomed Eng 20:171-210
Spitzer, K W; Bridge, J H (1992) Relationship between intracellular pH and tension development in resting ventricular muscle and myocytes. Am J Physiol 262:C316-27

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