Repolarization abnormalities and their arrhythmogenic consequences in porcine tachycardia-induced cardiomyopathy
Abstract
OBJECTIVES: Action potential prolongation related to the alteration of several membrane currents is constantly reported in heart failure (HF) but reports about its role in arrhythmogenesis are sparse. Our aim was to determine, by analogy with long QT syndromes, whether prolonged repolarization is associated with increased dispersion or linked to bradycardia-dependent ventricular arrhythmias in pacing-induced cardiomyopathy. METHODS: QT intervals, action potentials and transmural activation-to-recovery intervals (ARIs) along with whole-cell delayed rectifier (I(K)) and transient outward (I(to1)) K+ currents were recorded in left ventricle from pigs with HF and controls. HF was obtained after 14 days of rapid pacing at 250 ms. RESULTS: Repolarization was delayed as indexed by corrected QT intervals (13.7% increase, P<0.01) or ARIs (252+/-4 to 340+/-7 ms, P<0.01). ARIs were uniformly prolonged with disappearance of the transmural gradient, spatial dispersion of repolarization decreased by 50% (P<0.05). I(to1) density was reduced in HF from 1.35+/-0.1 to 0.57+/-0.04 pA/pF subepicardially, from 1.05+/-0.19 to 0.55+/-0.08 pA/pF midmyocardially and from 1.04+/-0.1 to 0.48+/-0.04 pA/pF subendocardially. I(K) density was significantly decreased in HF pigs vs. controls: subepicardially from 0.46+/-0.04 to 0.22+/-0.02 pA/pF; midmyocardially from 0.46+/-0.05 to 0.25+/-0.03 pA/pF; and subendocardially from 0.49+/-0.04 to 0.20+/-0.04 pA/pF following depolarization at +50 mV. Electrocardiogram (ECG) monitoring at the time of death did not disclose any polymorphic ventricular tachyarrhythmia. CONCLUSION: Despite a profound alteration in K+ currents, repolarization is uniformly prolonged in this model with no proclivity to develop bradycardia-dependent arrhythmias.
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Other differences between swine and human include small or lack of transient outward current (Ito) in swine and purkinje fiber distribution.
“Other differences include small or lack of transient outward current (Ito) in swine (Lacroix, et al., 2002; G. R. Li, et al., 2003; Schultz, et al., 2007) and purkinje fiber distribution (Hamlin, 2007).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Lacroix, et al., 2002
Heart failure can be induced in swine by rapid pacing and myocardial infarction.
“Heart failure can be induced in swine by a variety of methods such as rapid pacing (Lacroix, et al., 2002) and myocardial infarction (Pleger, et al., 2011).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Lacroix, et al., 2002
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- Authors
- Lacroix, D.
- Affiliations
- Université de Lille (FR)
- Corresponding author
- Lacroix, D
- Venue
- Cardiovascular Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-04
- Volume
- 54
- Issue
- 1
- Pages
- 42-50
- ISSN
- 0008-6363 (ISSN-L)
- OpenAlex
- W2081347317
- Cited by
- 37
- References
- 29
- Citations by year
- 2025: 1 · 2023: 1 · 2021: 1 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 4 · 2013: 3 · 2012: 1
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cardiovascular Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Keywords
- repolarization abnormalities, pacing-induced cardiomyopathy, heart failure, action potential prolongation, delayed rectifier potassium current, transient outward potassium current, transmural dispersion of repolarization, activation-recovery interval, ventricular arrhythmias, QT interval, potassium currents, porcine model, tachycardia-induced cardiomyopathy, arrhythmogenesis, long QT syndrome
- MeSH terms
- Action Potentials, Analysis of Variance, Animals, Cardiac Pacing, Artificial, Electrocardiography, Heart Failure, Long QT Syndrome, Perfusion, Swine, Patch-Clamp Techniques, Ventricular Remodeling, Models, Animal, Potassium Channels, Inwardly Rectifying, In Vitro Techniques
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