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Basis for the Induction of Tissue-Level Phase-2 Reentry as a Repolarization Disorder in the Brugada Syndrome.

Bueno-Orovio A, Cherry EM, Evans SJ, Fenton FH - Biomed Res Int (2015)

Bottom Line: Methods.In one-dimensional cables, P2R can be induced by adjoining lost-dome and delayed-dome regions, as mediated by tissue excitability and transmembrane voltage profiles, and reduced coupling facilitates its induction.Conclusions.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, University of Oxford, Oxford OX1 3QD, UK.

ABSTRACT
Aims. Human action potentials in the Brugada syndrome have been characterized by delayed or even complete loss of dome formation, especially in the right ventricular epicardial layers. Such a repolarization pattern is believed to trigger phase-2 reentry (P2R); however, little is known about the conditions necessary for its initiation. This study aims to determine the specific mechanisms that facilitate P2R induction in Brugada-affected cardiac tissue in humans. Methods. Ionic models for Brugada syndrome in human epicardial cells were developed and used to study the induction of P2R in cables, sheets, and a three-dimensional model of the right ventricular free wall. Results. In one-dimensional cables, P2R can be induced by adjoining lost-dome and delayed-dome regions, as mediated by tissue excitability and transmembrane voltage profiles, and reduced coupling facilitates its induction. In two and three dimensions, sustained reentry can arise when three regions (delayed-dome, lost-dome, and normal epicardium) are present. Conclusions. Not only does P2R induction by Brugada syndrome require regions of action potential with delayed-dome and lost-dome, but in order to generate a sustained reentry from a triggered waveback multiple factors are necessary, including heterogeneity in action potential distribution, tissue coupling, direction of stimulation, the shape of the late plateau, the duration of lost-dome action potentials, and recovery of tissue excitability, which is predominantly modulated by tissue coupling.

No MeSH data available.


Related in: MedlinePlus

Induction of reentrant activity by phase-2 reentry (P2R) in the right ventricular free wall. Under endocardial stimulation, the Brugada epicardial delayed-dome region is able to initiate P2R in the lost-dome region (t = 135 ms). The P2R wavefront propagates from apex to base (t = 175 ms), where it reexcites the recovered endocardial layer (t = 240 ms). Afterwards, reentry develops transmurally (t = 300–440 ms). Epicardial and endocardial views of the right ventricular free wall are provided. Color bar denotes transmembrane potential. Epicardial regions are as follows: lost-dome Brugada, upper left; late-dome Brugada, lower left; and normal, right.
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Related In: Results  -  Collection


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fig5: Induction of reentrant activity by phase-2 reentry (P2R) in the right ventricular free wall. Under endocardial stimulation, the Brugada epicardial delayed-dome region is able to initiate P2R in the lost-dome region (t = 135 ms). The P2R wavefront propagates from apex to base (t = 175 ms), where it reexcites the recovered endocardial layer (t = 240 ms). Afterwards, reentry develops transmurally (t = 300–440 ms). Epicardial and endocardial views of the right ventricular free wall are provided. Color bar denotes transmembrane potential. Epicardial regions are as follows: lost-dome Brugada, upper left; late-dome Brugada, lower left; and normal, right.

Mentions: P2R can also initiate reentrant activity in reconstructed three-dimensional ventricular wall preparations, as shown in Figure 5. A distribution of normal and BrS epicardial regions, similar to that of the two-dimensional case, was used together with normal endocardial and midmyocardial cells and was incorporated into a model of the canine right ventricular free wall extracted from a full ventricular model [35]. Following endocardial stimulation of the ventricular wall, the entire epicardium is excited nearly simultaneously. However, the shorter APs in the lost-dome region recover quickly, and the delayed-dome region is able to initiate P2R, which propagates within the lost-dome region. The P2R wavefront is then able to reexcite the recovered endocardial tissue at the base of the ventricle, and reentry develops transmurally, newly activating the entire midmyocardial and epicardial ventricular layers.


Basis for the Induction of Tissue-Level Phase-2 Reentry as a Repolarization Disorder in the Brugada Syndrome.

Bueno-Orovio A, Cherry EM, Evans SJ, Fenton FH - Biomed Res Int (2015)

Induction of reentrant activity by phase-2 reentry (P2R) in the right ventricular free wall. Under endocardial stimulation, the Brugada epicardial delayed-dome region is able to initiate P2R in the lost-dome region (t = 135 ms). The P2R wavefront propagates from apex to base (t = 175 ms), where it reexcites the recovered endocardial layer (t = 240 ms). Afterwards, reentry develops transmurally (t = 300–440 ms). Epicardial and endocardial views of the right ventricular free wall are provided. Color bar denotes transmembrane potential. Epicardial regions are as follows: lost-dome Brugada, upper left; late-dome Brugada, lower left; and normal, right.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4637010&req=5

fig5: Induction of reentrant activity by phase-2 reentry (P2R) in the right ventricular free wall. Under endocardial stimulation, the Brugada epicardial delayed-dome region is able to initiate P2R in the lost-dome region (t = 135 ms). The P2R wavefront propagates from apex to base (t = 175 ms), where it reexcites the recovered endocardial layer (t = 240 ms). Afterwards, reentry develops transmurally (t = 300–440 ms). Epicardial and endocardial views of the right ventricular free wall are provided. Color bar denotes transmembrane potential. Epicardial regions are as follows: lost-dome Brugada, upper left; late-dome Brugada, lower left; and normal, right.
Mentions: P2R can also initiate reentrant activity in reconstructed three-dimensional ventricular wall preparations, as shown in Figure 5. A distribution of normal and BrS epicardial regions, similar to that of the two-dimensional case, was used together with normal endocardial and midmyocardial cells and was incorporated into a model of the canine right ventricular free wall extracted from a full ventricular model [35]. Following endocardial stimulation of the ventricular wall, the entire epicardium is excited nearly simultaneously. However, the shorter APs in the lost-dome region recover quickly, and the delayed-dome region is able to initiate P2R, which propagates within the lost-dome region. The P2R wavefront is then able to reexcite the recovered endocardial tissue at the base of the ventricle, and reentry develops transmurally, newly activating the entire midmyocardial and epicardial ventricular layers.

Bottom Line: Methods.In one-dimensional cables, P2R can be induced by adjoining lost-dome and delayed-dome regions, as mediated by tissue excitability and transmembrane voltage profiles, and reduced coupling facilitates its induction.Conclusions.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, University of Oxford, Oxford OX1 3QD, UK.

ABSTRACT
Aims. Human action potentials in the Brugada syndrome have been characterized by delayed or even complete loss of dome formation, especially in the right ventricular epicardial layers. Such a repolarization pattern is believed to trigger phase-2 reentry (P2R); however, little is known about the conditions necessary for its initiation. This study aims to determine the specific mechanisms that facilitate P2R induction in Brugada-affected cardiac tissue in humans. Methods. Ionic models for Brugada syndrome in human epicardial cells were developed and used to study the induction of P2R in cables, sheets, and a three-dimensional model of the right ventricular free wall. Results. In one-dimensional cables, P2R can be induced by adjoining lost-dome and delayed-dome regions, as mediated by tissue excitability and transmembrane voltage profiles, and reduced coupling facilitates its induction. In two and three dimensions, sustained reentry can arise when three regions (delayed-dome, lost-dome, and normal epicardium) are present. Conclusions. Not only does P2R induction by Brugada syndrome require regions of action potential with delayed-dome and lost-dome, but in order to generate a sustained reentry from a triggered waveback multiple factors are necessary, including heterogeneity in action potential distribution, tissue coupling, direction of stimulation, the shape of the late plateau, the duration of lost-dome action potentials, and recovery of tissue excitability, which is predominantly modulated by tissue coupling.

No MeSH data available.


Related in: MedlinePlus