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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

Space-time plots and wave profiles for three cases of phase-2 reentry (P2R) in one-dimensional epicardial cables. (a) Antidromic (retrograde) P2R generated by a propagating wave initiated from the lost-dome region (red) using Model 1. (b) Orthodromic (forward) P2R generated by a propagating wave initiated from the delayed-dome region (blue) using Model 1. (c) Antidromic P2R generated by a propagating wave initiated from the lost-dome region (red) using Model 2. In all cases, P2R originates slightly away from the interface between the lost-dome and delayed-dome regions (horizontal scale bar, 1 cm).
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fig2: Space-time plots and wave profiles for three cases of phase-2 reentry (P2R) in one-dimensional epicardial cables. (a) Antidromic (retrograde) P2R generated by a propagating wave initiated from the lost-dome region (red) using Model 1. (b) Orthodromic (forward) P2R generated by a propagating wave initiated from the delayed-dome region (blue) using Model 1. (c) Antidromic P2R generated by a propagating wave initiated from the lost-dome region (red) using Model 2. In all cases, P2R originates slightly away from the interface between the lost-dome and delayed-dome regions (horizontal scale bar, 1 cm).

Mentions: Using the formulations for prolonged and abbreviated APs, P2R can be induced in our BrS models in a one-dimensional cable (see Figure 2) containing a region where the dome is lost adjoining a region where the dome is delayed. In Figure 2(a), the cable is stimulated from the lost-dome region. Because the APs in this region are particularly short, large voltage gradients arise in the interface between lost-dome and delayed-dome regions. If the lost-dome region recovers from its AP while the delayed-dome region remains depolarized, diffusive currents can bring the recovered delayed-dome region above threshold and initiate a second propagating pulse, which is the P2R. In this case the P2R is antidromic, with propagation in the lost-dome region occurring in the opposite direction of the initial activation. P2R also can be orthodromic, as shown in Figure 2(b). In this case, the cable is stimulated from the delayed-dome region. The APs in the lost-dome region are short enough that the delayed-dome region is still sufficiently depolarized to initiate a second pulse after the lost-dome region has recovered. Model 2 is able to produce P2R in the same manner, as shown in the antidromic example in Figure 2(c).


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)

Space-time plots and wave profiles for three cases of phase-2 reentry (P2R) in one-dimensional epicardial cables. (a) Antidromic (retrograde) P2R generated by a propagating wave initiated from the lost-dome region (red) using Model 1. (b) Orthodromic (forward) P2R generated by a propagating wave initiated from the delayed-dome region (blue) using Model 1. (c) Antidromic P2R generated by a propagating wave initiated from the lost-dome region (red) using Model 2. In all cases, P2R originates slightly away from the interface between the lost-dome and delayed-dome regions (horizontal scale bar, 1 cm).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: Space-time plots and wave profiles for three cases of phase-2 reentry (P2R) in one-dimensional epicardial cables. (a) Antidromic (retrograde) P2R generated by a propagating wave initiated from the lost-dome region (red) using Model 1. (b) Orthodromic (forward) P2R generated by a propagating wave initiated from the delayed-dome region (blue) using Model 1. (c) Antidromic P2R generated by a propagating wave initiated from the lost-dome region (red) using Model 2. In all cases, P2R originates slightly away from the interface between the lost-dome and delayed-dome regions (horizontal scale bar, 1 cm).
Mentions: Using the formulations for prolonged and abbreviated APs, P2R can be induced in our BrS models in a one-dimensional cable (see Figure 2) containing a region where the dome is lost adjoining a region where the dome is delayed. In Figure 2(a), the cable is stimulated from the lost-dome region. Because the APs in this region are particularly short, large voltage gradients arise in the interface between lost-dome and delayed-dome regions. If the lost-dome region recovers from its AP while the delayed-dome region remains depolarized, diffusive currents can bring the recovered delayed-dome region above threshold and initiate a second propagating pulse, which is the P2R. In this case the P2R is antidromic, with propagation in the lost-dome region occurring in the opposite direction of the initial activation. P2R also can be orthodromic, as shown in Figure 2(b). In this case, the cable is stimulated from the delayed-dome region. The APs in the lost-dome region are short enough that the delayed-dome region is still sufficiently depolarized to initiate a second pulse after the lost-dome region has recovered. Model 2 is able to produce P2R in the same manner, as shown in the antidromic example in Figure 2(c).

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