SPATIAL DISPERSION OF REPOLARISATION AND VULNERABILITY TO RE-ENTRY IN CARDIAC TISSUE: A MODEL STUDY

University of Oxford (2004) J Physiol 561P, PC21

Communications: SPATIAL DISPERSION OF REPOLARISATION AND VULNERABILITY TO RE-ENTRY IN CARDIAC TISSUE: A MODEL STUDY

Clayton,Richard ; Holden,Arun V;

1. Department of Computer Science, University of Sheffield, Sheffield, United Kingdom. 2. School of Biomedical Sciences, University of Leeds, Leeds, United Kingdom.

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Re-entrant arrhythmias are more likely to be induced in cardiac tissue with regional differences in action potential duration (APD). However, electrotonic current flow during repolarisation can mask regions with prolonged or shortened APD, and so measured APD dispersion may not reflect intrinsic regional differences in repolarisation. In this study we used a virtual cardiac tissue to investigate how intrinsic regional differences in repolarisation can influence both measures of APD dispersion and vulnerability to re-entry following a premature stimulus. We used the LuoRudy1 model for ventricular cells (Luo and Rudy 1991) in which repolarisation is dominated by a single K+ current. We set up 60 x 60 mm 2D virtual tissues (Clayton 2001) in which the central 40 x 40 mm region was heterogenous and made up from square regions with alternating short and long APD given by high (0.4 mS cm-2) and low (between 0.1 and 0.3 mS cm-2) maximal K+ conductance (gKmax) respectively. We fixed gKmax in the surrounding tissue to be 0.4 mS cm-2. We varied (i) the spatial scale of heterogeneity between 20 mm and 5 mm, (ii) gKmax of long APD regions between 0.1 and 0.3 mS cm-2, and (iii) the diffusion coefficient from 0.1 cm2 ms-1 to 0.05 and 0.2 cm2 ms-1. We measured the range of APD in each of these virtual tissues (APD dispersion) during pacing along one edge at intervals of 500 ms, and also the vulnerability to re-entry by a premature stimulus delivered along the same edge. The results are shown in the table. As the spatial scale of regional differences increased, both APD dispersion and the width of the vulnerable period increased in a linear fashion. Increasing gKmax in the long APD regions (i.e. reducing APD in these regions) resulted in reduced APD dispersion and a narrower vulnerable window. Increasing and decreasing the diffusion coefficient by a factor of two also decreased and increased APD dispersion respectively. Overall there was a well correlated linear relationship between APD dispersion and width of the vulnerable window. We conclude that although electrotonic effects can mask intrinsic regional differences in repolarisation, they also act to narrow the vulnerable period for re-entry. Thus APD dispersion provides a good estimate of vulnerability to re-entry.



Where applicable, experiments conform with Society ethical requirements.

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