Early repolarization in mice causes overestimation of ventricular activation time by the QRS duration

Boukens, Bastiaan J.; Hoogendijk, Mark G.; Verkerk, Arie O.; Linnenbank, André C.; Dam, Peter van; Remme, CA; Fiolet, J.W.T.; Opthof, Tobias; Christoffels, Vincent M.; Coronel, Ruben

doi:10.1093/cvr/cvs299

Cited by 41 publications

(72 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The start of the QRS complex was defined as the earliest moment of deviation from baseline. The end of the QRS complex determined in lead III and was defined as the moment when the S wave returned to the isoelectric line (Boukens et al, 2013). We determined the end of the T wave by the tangent method (Lepeschkin and Surawicz, 1952).…”

Section: Methodsmentioning

confidence: 99%

Alk3 mediated Bmp signaling controls the contribution of epicardially derived cells to the tissues of the atrioventricular junction

Lockhart

Boukens

Phelps

et al. 2014

Developmental Biology

View full text Add to dashboard Cite

Recent studies using mouse models for cell fate tracing of epicardial derived cells (EPDCs) have demonstrated that at the atrioventricular (AV) junction EPDCs contribute to the mesenchyme of the AV sulcus, the annulus fibrosus, and the parietal leaflets of the AV valves. There is little insight, however, into the mechanisms that govern the contribution of EPDCs to these tissues. While it has been demonstrated that bone morphogenetic protein (Bmp) signaling is required for AV cushion formation, its role in regulating EPDC contribution to the AV junction remains unexplored. To determine the role of Bmp signaling in the contribution of EPDCs to the AV junction, the Bmp receptor activin-like kinase 3 (Alk3; or Bmpr1a) was conditionally deleted in the epicardium and EPDCs using the mWt1/IRES/GFP-Cre (Wt1Cre) mouse. Embryonic Wt1Cre;Alk3fl/fl specimens showed a significantly smaller AV sulcus and a severely underdeveloped annulus fibrosus. Electrophysiological analysis of adult Wt1Cre;Alk3fl/fl mice showed, unexpectedly, no ventricular pre-excitation. Cell fate tracing revealed a significant decrease in the number of EPDCs within the parietal leaflets of the AV valves. Postnatal Wt1Cre;Alk3fl/fl specimens showed myxomatous changes in the leaflets of the mitral valve. Together these observations indicate that Alk3 mediated Bmp signaling is important in the cascade of events that regulate the contribution of EPDCs to the AV sulcus, annulus fibrosus, and the parietal leaflets of the AV valves. Furthermore, this study shows that EPDCs do not only play a critical role in early developmental events at the AV junction, but that they also are important in the normal maturation of the AV valves.

show abstract

Section: Methodsmentioning

confidence: 99%

Alk3 mediated Bmp signaling controls the contribution of epicardially derived cells to the tissues of the atrioventricular junction

Lockhart

Boukens

Phelps

et al. 2014

Developmental Biology

View full text Add to dashboard Cite

show abstract

“…VEGF-B TG hearts show two distinct ECG changes. First is increase in the width of the QRSp which together with unaffected QRS represents prolongation of early repolarization (Liu et al, 2004; Boukens et al, 2013, 2014). That prolongation fits very good to lengthening of APD 60–70 which we observed in TG cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

“…That change of QRSp is common to LVH (Merentie et al, 2015) and some forms of sodium channelopathies (Remme et al, 2006; Watanabe et al, 2011). And second is decreased amplitude of the R and S waves, which has been shown to associate with acute infarction or ischemia in mouse heart (Gehrmann et al, 2001; Merentie et al, 2015) and e.g., sodium channel blocker Ajmaline (Boukens et al, 2013). VEGF-B TG hearts show only modest signs of organ level hypertrophy and no infarctions, so that the ECG anomalies cannot be considered as signs of cardiac disease, but they rather reflect more specific changes in cardiomyocytes electrophysiology.…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart

et al. 2017

View full text Add to dashboard Cite

Vascular endothelial growth factor B (VEGF-B) is a potent mediator of vascular, metabolic, growth, and stress responses in the heart, but the effects on cardiac muscle and cardiomyocyte function are not known. The purpose of this study was to assess the effects of VEGF-B on the energy metabolism, contractile, and electrophysiological properties of mouse cardiac muscle and cardiac muscle cells. In vivo and ex vivo analysis of cardiac-specific VEGF-B TG mice indicated that the contractile function of the TG hearts was normal. Neither the oxidative metabolism of isolated TG cardiomyocytes nor their energy substrate preference showed any difference to WT cardiomyocytes. Similarly, myocyte Ca2+ signaling showed only minor changes compared to WT myocytes. However, VEGF-B overexpression induced a distinct electrophysiological phenotype characterized by ECG changes such as an increase in QRSp time and decreases in S and R amplitudes. At the level of isolated TG cardiomyocytes, these changes were accompanied with decreased action potential upstroke velocity and increased duration (APD60–70). These changes were partly caused by downregulation of sodium current (INa) due to reduced expression of Nav1.5. Furthermore, TG myocytes had alterations in voltage-gated K+ currents, namely decreased density of transient outward current (Ito) and total K+ current (Ipeak). At the level of transcription, these were accompanied by downregulation of Kv channel-interacting protein 2 (Kcnip2), a known modulatory subunit for Kv4.2/3 channel. Cardiac VEGF-B overexpression induces a distinct electrophysiological phenotype including remodeling of cardiomyocyte ion currents, which in turn induce changes in action potential waveform and ECG.

show abstract

“…However, recent investigators defined the end of QRS complex at the end of J-wave [30]. Optical mapping studies showed that ventricular activation in mice lasts until the very end of the J-wave [16; 31]. To address this problem, we studied two QRS segments: one ending at J-peak, and another ending at J-end.…”

Section: Discussionmentioning

confidence: 99%

Correlation between the high-frequency content of the QRS on murine surface electrocardiogram and the sympathetic nerves density in left ventricle after myocardial infarction: Experimental study

Sedaghat

Gardner

Kabir

et al. 2017

Journal of Electrocardiology

View full text Add to dashboard Cite

Denervated post-infarct scar is arrhythmogenic. Our aim was to compare QRS frequency content in denervated and innervated left ventricular (LV) scar. In-vivo single lead ECG telemetry device was implanted in 17 heterozygous PTPσ (HET) and 7 lacking PTPσ (KO) transgenic mice. Myocardial infarction (MI) with reperfusion and sham surgery was performed. HET mice developed a denervated scar, whereas KO mice developed innervated scar. The power spectral density was used to assess the QRS frequency content. Denervated as compared to innervated post-MI scar was characterized by the higher relative contribution of 300–500Hz (14±1 vs. 9±1%; P=0.001) but reduced relative contribution of 200–300 Hz (86±1 vs. 91±1%; P=0.001). Norepinephrine concentration in peri-infarct zone correlated with both 1–200 Hz (r=0.75; p=0.03) and 200–500 Hz QRS power (r=0.73;P=0.04). Sympathetic fiber density within the infarct correlated with 200–300/200–500 Hz QRS power ratio (r=0.56;P=0.005). Intracellular sigma peptide injections in post-MI HET mice restored the QRS power.

show abstract

Early repolarization in mice causes overestimation of ventricular activation time by the QRS duration

Cited by 41 publications

References 31 publications

Alk3 mediated Bmp signaling controls the contribution of epicardially derived cells to the tissues of the atrioventricular junction

Alk3 mediated Bmp signaling controls the contribution of epicardially derived cells to the tissues of the atrioventricular junction

Vascular Endothelial Growth Factor-B Induces a Distinct Electrophysiological Phenotype in Mouse Heart

Correlation between the high-frequency content of the QRS on murine surface electrocardiogram and the sympathetic nerves density in left ventricle after myocardial infarction: Experimental study

Contact Info

Product

Resources

About