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Ionic mechanisms of electrophysiological heterogeneity and conduction block in the infarct border zone.

ABSTRACT: The increased incidence of arrhythmia in the healing phase after infarction has been linked to remodeling in the epicardial border zone (EBZ). Ionic models of normal zone (NZ) and EBZ myocytes were incorporated into one-dimensional models of propagation to gain mechanistic insights into how ion channel remodeling affects action potential (AP) duration (APD) and refractoriness, vulnerability to conduction block, and conduction safety postinfarction. We found that EBZ tissue exhibited abnormal APD restitution. The remodeled Na(+) current (I(Na)) and L-type Ca(2+) current (I(Ca,L)) promoted increased effective refractory period and prolonged APD at a short diastolic interval. While postrepolarization refractoriness due to remodeled EBZ I(Na) was the primary determinant of the vulnerable window for conduction block at the NZ-to-EBZ transition in response to premature S2 stimuli, altered EBZ restitution also promoted APD dispersion and increased the vulnerable window at fast S1 pacing rates. Abnormal EBZ APD restitution and refractoriness also led to abnormal periodic conduction block patterns for a range of fast S1 pacing rates. In addition, we found that I(Na) remodeling decreased conduction safety in the EBZ but that inward rectifier K(+) current remodeling partially offset this decrease. EBZ conduction was characterized by a weakened AP upstroke and short intercellular delays, which prevented I(Ca,L) and transient outward K(+) current remodeling from playing a role in EBZ conduction in uncoupled tissue. Simulations of a skeletal muscle Na(+) channel SkM1-I(Na) injection into the EBZ suggested that this recently proposed antiarrhythmic therapy has several desirable effects, including normalization of EBZ effective refractory period and APD restitution, elimination of vulnerability to conduction block, and normalization of conduction in tissue with reduced intercellular coupling.

SUBMITTER: Decker KF

PROVIDER: S-EPMC2993197 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Ionic mechanisms of electrophysiological heterogeneity and conduction block in the infarct border zone.

Decker Keith F KF Rudy Yoram Y

American journal of physiology. Heart and circulatory physiology 20100813 5

The increased incidence of arrhythmia in the healing phase after infarction has been linked to remodeling in the epicardial border zone (EBZ). Ionic models of normal zone (NZ) and EBZ myocytes were incorporated into one-dimensional models of propagation to gain mechanistic insights into how ion channel remodeling affects action potential (AP) duration (APD) and refractoriness, vulnerability to conduction block, and conduction safety postinfarction. We found that EBZ tissue exhibited abnormal APD ...[more]

PMID: 20709867

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Project description:Introduction: Computational models of the heart increasingly require detailed microstructural information to capture the impact of tissue remodeling on cardiac electromechanics in, for example, hearts with myocardial infarctions. Myocardial infarctions are surrounded by the infarct border zone (BZ), which is a site of electromechanical property transition. Magnetic resonance imaging (MRI) is an emerging method for characterizing microstructural remodeling and focal myocardial infarcts and the BZ can be identified with late gadolinium enhanced (LGE) MRI. Microstructural remodeling within the BZ, however, remains poorly characterized by MRI due, in part, to the fact that LGE and DT-MRI are not always available for the same heart. Diffusion tensor MRI (DT-MRI) can evaluate microstructural remodeling by quantifying the DT apparent diffusion coefficient (ADC, increased with decreased cellularity), fractional anisotropy (FA, decreased with increased fibrosis), and tissue mode (decreased with increased fiber disarray). The purpose of this work was to use LGE MRI in post-infarct porcine hearts (N = 7) to segment remote, BZ, and infarcted myocardium, thereby providing a basis to quantify microstructural remodeling in the BZ and infarcted regions using co-registered DT-MRI. Methods: Chronic porcine infarcts were created by balloon occlusion of the LCx. 6-8 weeks post-infarction, MRI contrast was administered, and the heart was potassium arrested, excised, and imaged with LGE MRI (0.33 × 0.33 × 0.33 mm) and co-registered DT-MRI (1 × 1 × 3 mm). Myocardium was segmented as remote, BZ, or infarct by LGE signal intensity thresholds. DT invariants were used to evaluate microstructural remodeling by quantifying ADC, FA, and tissue mode. Results: The BZ significantly remodeled compared to both infarct and remote myocardium. BZ demonstrated a significant decrease in cellularity (increased ADC), significant decrease in tissue organization (decreased FA), and a significant increase in fiber disarray (decreased tissue mode) relative to remote myocardium (all p < 0.05). Microstructural remodeling in the infarct was similar, but significantly larger in magnitude (all p < 0.05). Conclusion: DT-MRI can identify regions of significant microstructural remodeling in the BZ that are distinct from both remote and infarcted myocardium.

Dataset Information

Ionic mechanisms of electrophysiological heterogeneity and conduction block in the infarct border zone.

Publications

Ionic mechanisms of electrophysiological heterogeneity and conduction block in the infarct border zone.

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