| TITLE |
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Regional Ischemia in 2D |
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| AUTHORS |
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Brock Tice,
Blanca Rodríguez,
James
Eason,
Felipe Aguel,
and
Natalia
Trayanova |
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| ABSTRACT |
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Using computational models based
on realistic ion channel dynamics,
tissue conduction, and tissue morphology, it is possible to gain
detailed mechanistic insight into conduction patterns in the
heart. In this study, we develop 2D and 3D models of the regionally
ischemic ventricles. The goal of this study is to generate and
validate a model of ischemia phase 1A following occlusion of the left
anterior descending (LAD) coronary artery, and use the model to study
the mechanisms of arrhythmogenesis in ischemia.
In this study only the 2D model is used for simulation, in order to
first observe mechanisms in a simpler model. A 4-sided boundary is
defined about the region perfused by the LAD. Ischemic influence is
considered to extend inward from the borders of this region with a
linear profile to the central ischemic zone. Ischemia is modeled as
resulting from hypoxia, acidosis, and hyperkalemia of varying degrees
(0-10min of occlusion). Conduction is modeled using FEM software
which accomodates heterogeneous ischemic characteristics. Pacing is
applied to the left ventricle at a range of regular rates from normal
(300 ms cycle length) to tachyarrhythmic (175 ms cycle length) in an
effort to elicit reentrant behavior. A premature stimulus similar to
an ectopic activation is applied 155 ms after the last pacing
stimulus. We examine ischemia-induced alterations in action potential
duration, refractoriness, and propagation in order to investigate
mechanisms of reentry initiation under these conditions.
Reentry occurred only when the ischemic zone was severely ischemic;
propagation blocked there as well as in the lateral border zone (BZ). Conduction
continued in the epi/endocardial BZs, however, it was characterized
with alternans in both amplitude and duration. The alternans
increased upon increase in pacing rate and decrease in
epi/endocardial BZ width. At cycle lengths below 200ms and BZ widths
below 0.5mm, propagation blocked in the left ventricle and septum,
and reentered through the right-ventricular wall. Further decrease in
epi/endocardial BZ width led to conduction failure there and thus
failure to initiate reentry.
Simulation study found regional ischemia as-modeled to be both valid
with respect to previous experimental results, and useful for
providing new mechanistic insight into arrhythmogenesis in the
diseased heart. Specifically, border-zone alternans were found to
lead to unidirectional block and initiation of reentrant conduction.
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| FIGURES |
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© CCEL 2005
Johns Hopkins University |
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< < Click on the image to enlarge!
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| MOVIES |
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© CCEL 2005
Johns Hopkins University |
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< < Click on the image to play the video!
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Uniform reentry subsequent to block in the anterior septum. |
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© CCEL 2005
Johns Hopkins University |
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< < Click on the image to play the video!
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Nonuniform reentry subsequent to block in the RV free wall following
premature stimulus. The simulation shown includes transmural
heterogeneity of action potential duration in the ischemic region. |
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