Pro-Arrhythmic Ventricular Remodeling Is Associated With Increased Respiratory and Low-Frequency Oscillations of Monophasic Action Potential Duration in the Chronic Atrioventricular Block Dog Model.

David Jaap Sprenkeler,Marc A Vos,Alexandre Bossu,Albert Dunnink,Jet D M Beekman

doi:10.3389/fphys.2019.01095

David Jaap Sprenkeler, Marc A Vos + Show 3 more

Open Access

https://doi.org/10.3389/fphys.2019.01095

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Journal: Frontiers in physiology	Publication Date: Aug 23, 2019
Citations: 9	License type: CC BY 4.0

Affiliation: University Medical Center Utrecht

Abstract

In addition to beat-to-beat fluctuations, action potential duration (APD) oscillates at (1) a respiratory frequency and (2) a low frequency (LF) (<0.1 Hz), probably caused by bursts of sympathetic nervous system discharge. This study investigates whether ventricular remodeling in the chronic AV block (CAVB) dog alters these oscillations of APD and whether this has consequences for arrhythmogenesis. We performed a retrospective analysis of 39 dog experiments in sinus rhythm (SR), acute AV block (AAVB), and after 2 weeks of chronic AV block. Spectral analysis of left ventricular monophasic action potential duration (LV MAPD) was done to quantify respiratory frequency (RF) power and LF power. Dofetilide (0.025 mg/kg in 5 min) was infused to test for inducibility of Torsade de Pointes (TdP) arrhythmias. RF power was significantly increased at CAVB compared to AAVB and SR (log[RF] of −1.13 ± 1.62 at CAVB vs. log[RF] of −2.82 ± 1.24 and −3.29 ± 1.29 at SR and AAVB, respectively, p < 0.001). LF power was already significantly increased at AAVB and increased even further at CAVB (−3.91 ± 0.70 at SR vs. −2.52 ± 0.85 at AAVB and −1.14 ± 1.62 at CAVB, p < 0.001). In addition, LF power was significantly larger in inducible CAVB dogs (log[LF] −0.6 ± 1.54 in inducible dogs vs. −2.56 ± 0.43 in non-inducible dogs, p < 0.001). In conclusion, ventricular remodeling in the CAVB dog results in augmentation of respiratory and low-frequency (LF) oscillations of LV MAPD. Furthermore, TdP-inducible CAVB dogs show increased LF power.

Highlights

Repolarization lability, quantified as beat-to-beat fluctuations in action potential duration (APD), is known to contribute to arrhythmogenesis (Thomsen et al, 2004, 2007)
In chronic AV block (CAVB), electrical remodeling has occurred as seen by a significant increase in QT, QT-interval was corrected for heart rate (QTc), and left ventricular monophasic action potential duration (LV monophasic action potential duration (MAPD))
Short-term variability (STV) appears to be higher in the inducible dogs; this did not reach statistical significance (p = 0.08)

Summary

Introduction

Repolarization lability, quantified as beat-to-beat fluctuations in action potential duration (APD), is known to contribute to arrhythmogenesis (Thomsen et al, 2004, 2007). An increased beatto-beat repolarization variability has been found in patients with a high risk of ventricular arrhythmias, such as patients with heart failure (Berger et al, 1997; Hinterseer et al, 2010), Respiratory and Low-Frequency Oscillations ischemia (Murabayashi et al, 2002), long QT-syndrome (Hinterseer et al, 2008, 2009), hypertrophic cardiomyopathy (Atiga et al, 2000), or hypertension with left ventricular hypertrophy (Piccirillo et al, 2002). While a sympathetically mediated LF pattern of arterial blood pressure (known as Mayer waves) is well-known (Malpas, 2002), oscillations at 0.1 Hz have only recently been found in APD as well (Hanson et al, 2014; Porter et al, 2018) These fluctuations have been identified on the surface ECG as changes in T wave vector angle between consecutive beats, referred to as “periodic repolarization dynamics” (PRD; Rizas et al, 2014)

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