Dataset Information

Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia.

ABSTRACT:

Background

Anisotropic reentrant excitation occurs in the remodeled substrate of the epicardial border zone (EBZ) of the 5-day infarcted canine heart. Reentry is stabilized because of the formation of functional lines of block. We hypothesized that regional differences of ionic currents in cells of the EBZ form these lines of block. Therefore, we first mapped reentrant circuits of sustained tachycardias, then dispersed cells (infarct zone cells, IZs) from the central common pathway of the circuit (IZc) as well as from the other side of the line of block (outer pathway, IZo) for study.

Methods and results

We mapped reentrant circuits in the EBZ of infarcted hearts during sustained ventricular tachycardias (>30 seconds, n=17 episodes, cycle lengths=218+/-7.9 ms). INa density was reduced in both IZc and IZo, and the kinetic properties of IZc INa were markedly altered versus IZo. Structural remodeling of the sodium channel protein Nav1.5 occurred in IZs, with cell surface localization differing from normal cells. Both IZc and IZo have similar but reduced ICaL, whereas IZc showed changes in Ca2+ current kinetics with an acceleration of current decay. Computer simulations of the 2D EBZ showed that incorporating only differences between INa in IZc and IZo prevented stability of the reentrant circuit. Incorporating only differences between ICaL in the IZc and IZo cells also prevented stability of the circuit. However, incorporating both INa and ICaL current differences stabilized the simulated reentrant circuit, and lines of block formed between the 2 distinct regions.

Conclusions

Despite differences in INa and ICaL properties in cells of the center and outer pathways of a reentrant circuit, the resulting changes in effective refractory periods tend to stabilize reentry in this remodeled substrate.

SUBMITTER: Baba S

PROVIDER: S-EPMC4289139 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature

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Publications

Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia.

Baba Shigeo S Dun Wen W Cabo Candido C Boyden Penelope A PA

Circulation 20051003 16

<h4>Background</h4>Anisotropic reentrant excitation occurs in the remodeled substrate of the epicardial border zone (EBZ) of the 5-day infarcted canine heart. Reentry is stabilized because of the formation of functional lines of block. We hypothesized that regional differences of ionic currents in cells of the EBZ form these lines of block. Therefore, we first mapped reentrant circuits of sustained tachycardias, then dispersed cells (infarct zone cells, IZs) from the central common pathway of th ...[more]

PMID: 16203911

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Project description:BackgroundInfarct border zone (IBZ) geometry likely affects inducibility and characteristics of postinfarction reentrant ventricular tachycardia, but the connection has not been established.ObjectiveThe purpose of this study was to determine characteristics of postinfarction ventricular tachycardia in the IBZ.MethodsA geometric model describing the relationship between IBZ geometry and wavefront propagation in reentrant circuits was developed. Based on the formulation, slow conduction and block were expected to coincide with areas where IBZ thickness (T) is minimal and the local spatial gradient in thickness (DeltaT) is maximal, so that the degree of wavefront curvature rho proportional, variant DeltaT/T is maximal. Regions of fastest conduction velocity were predicted to coincide with areas of minimum DeltaT. In seven arrhythmogenic postinfarction canine heart experiments, tachycardia was induced by programmed stimulation, and activation maps were constructed from multichannel recordings. IBZ thickness was measured in excised hearts from histologic analysis or magnetic resonance imaging. Reentrant circuit properties were predicted from IBZ geometry and compared with ventricular activation maps after tachycardia induction.ResultsMean IBZ thickness was 231 +/- 140 microm at the reentry isthmus and 1440 +/- 770 microm in the outer pathway (P <0.001). Mean curvature rho was 1.63 +/- 0.45 mm(-1) at functional block line locations, 0.71 +/- 0.18 mm(-1) at isthmus entrance-exit points, and 0.33 +/- 0.13 mm(-1) in the outer reentrant circuit pathway. The mean conduction velocity about the circuit during reentrant tachycardia was 0.32 +/- 0.04 mm/ms at entrance-exit points, 0.42 +/- 0.13 mm/ms for the entire outer pathway, and 0.64 +/- 0.16 mm/ms at outer pathway regions with minimum DeltaT. Model sensitivity and specificity to detect isthmus location was 75.0% and 97.2%.ConclusionsReentrant circuit features as determined by activation mapping can be predicted on the basis of IBZ geometrical relationships.

Dataset Information

Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia.

Background

Methods and results

Conclusions

Publications

Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia.

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