Page 138 - Advances in Biomechanics and Tissue Regeneration

134 7. MULTISCALE NUMERICAL SIMULATION OF HEART ELECTROPHYSIOLOGY

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FIG. 7.11 Vulnerability window for different levels of [K ] o in a model without the washed-out zone. Early stimulation starts at point F in Fig. 7.6.

Our results indicate that reentrant activity may be in part sustained by the presence of a washed zone in the endo-
cardium, as suggested by Wilensky et al. [31]. In order to get a better insight into this, all the simulations were
repeated with a model without the washed zone. Fig. 7.11 shows the VW for the model without a washed zone
for an ectopic stimulation delivered at point F in Fig. 7.6. The most significant finding was that all the reentries
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self-terminated after two or threecompletecircuits. Whilefor [K ] o ¼ 7mN and [K ] o ¼ 8 mN the VW was the same
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but without sustained reentries, for [K ] o ¼ 9 mM, nonsustained reentrant activity was found for CIs between 310
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and 370 ms. The significant difference in the VW between [K ] o ¼ 9 mM and the other two lower concentrations is
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associated with the rapid increase in the ERP with [K ] o . On the contrary, the presence of a VW for [K ] o ¼ 9mM in
the model without the washed zone is due to the slower CV associated with the ischemic tissue in the endocardium,
which allows closing the reentrant circuit that otherwise will find the tissue within the refractory period. These
results suggest that the washed zone could act as a proarrhythmic substrate factor helping with establishing sus-
tained ventricular tachycardia.
A number of limitations are associated with this study. The Purkinje system was not present in our model because
we were interested in studying the mechanisms associated with reentry rather than in the biophysical mechanisms
leading to ectopic excitation. In particular, the study by Janse et al. [30] suggests that earlier activation is most likely
due to focal activity localized in the Purkinje fibers close to the ischemic BZ. Future studies, however, are intended to
extend our study to evaluate the implication of the Purkinje system in earlier activation during acute regional ischemia
and its potential role in contributing to arrhythmia. However, a recent study by Dutta et al. [58] indicates that early
activation causing transmural microreentry could be generated by electrotonically triggered EADs at the endocar-
dium. A second important limitation is related to the definition of the ischemic zone itself. We have considered an
idealized shape with smooth borders and transitions between the IZ and the NZ. Patient-specific acute regional ische-
mic areas are expected to have tortuous borders that may contribute to modify the evolution of the reentry patterns and
the VW. However, we believe that the general patterns that have emerged in this study will not be greatly modified by
the actual shape of the ischemic area as long as the general dimensions of the ischemic area are maintained. In addition,
we have only monitored the reentrant activity up to 3 s, during which we have observed perpetuating activity for a
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restricted vulnerable window. In some cases, that is, CI between 265 and 270 ms for [K ] o ¼ 7.0 mM, the reentrant
activity was spontaneously terminated after completing three reentrant circuits. This type of behavior was also
reported in Janse et al. [30], where tachycardia terminated within 30 s after initiation. Additional studies on larger
ischemic zones are required in order to determine if the size of the ischemic area may favor the onset of ventricular
fibrillation in the ischemic heart. In addition, the location of the ectopic activity is important for both the size of the
vulnerable window and the reentrant pattern.
In conclusion, the model predicts the generation of reentry within the ischemic zone due to the heterogeneity in the
refractory period between the ischemic affected area and the normal myocardium. The observed patterns obtained
with the simulations are in good agreement with experimental studies conducted in porcine and canine hearts sub-
jected to acute regional ischemia. The main results of the simulations can be summarized as follows: (i) As a conse-
quence of the applied extra stimulus that originates an ectopic beat, reentrant activity generated for CIs which range
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depends on the value of the extracellular potassium concentration [K ] o ; (ii) The reentrant activity, generated due to the
extra stimulus initiated as a consequence of the interaction between wavefronts, emerge from the washed zone into the
ischemic zone.

I. BIOMECHANICS