16 August 2011
4pm - 5pm
Venue: Ground Floor Seminar Room (G010), UniServices House, 70 Symonds Street, Auckland
A Bioengineering PhD Exit Seminar by Zoar Engleman, Auckland Bioengineering Institute
Mortality due to structural heart disease (SHD) remains high despite advances in clinical therapies. The aim of my thesis was to elucidate how structural remodeling in heart disease may lead to the development of potentially life threatening arrhythmias. This objective was advanced by the combined use of mathematical modelling and an experimental model of myocardial infarction (MI).
The computer model was used to investigate possible electrical effects of tissue remodelling associated with SHD. Heterogeneous discontinuities resembling patchy fibrosis were incorporated into a 2D array of coupled myocytes with uniform electrical properties. It was shown that structural discontinuities alone can alter dynamic instability and provide a rate-dependent substrate for electrical reentry. This challenges the wide-spread notion that dynamic instability of this kind is due to changes in cellular electrical properties.
Experimental studies were carried out in sheep with healed reperfusion MI. Intramural electrical activation in the infarct border zone (BZ) was recorded with a high density mapping array. Novel techniques were developed that enable the spread of activation in this region to be reconstructed in 3D at higher resolution than has previously been possible. Heart structure was also reconstructed in 3D using magnetic resonance imaging and serial histology. Intracardiac left ventricular mapping was carried out simultaneously.
The BZ substrate was characterised by systematic intramural pacing. This confirmed that activation delay, consistent with tortuous electrical pathways, is the origin of apparently slow conduction in the BZ. Stimulus-site specific, low-level activation in the BZ was followed by uniform propagation around the infarct boundary at relatively normal conduction velocities.
Electrical activity in the intramural BZ was recorded during induction and maintenance of ventricular tachycardia (VT). BZ activation delays were amplified during VT induction and in some cases contributed substantially to the cycle length during VT. For the first time, complex intramural activation patterns were tracked through the BZ during reentry. In general, local intramural and endocardial activation patterns were non-stationary during VT despite relatively monomorphic limb-lead electrocardiograms. This signifies a heterogeneous substrate capable of supporting multiple arrhythmic circuits.
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