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Article ; Online: Excitability and propagation of the electrical impulse in Venus flytrap; a comparative electrophysiological study of unipolar electrograms with myocardial tissue.

de Bakker, Jacques M T / Belterman, Charly N W / Coronel, Ruben

Bioelectrochemistry (Amsterdam, Netherlands)

2021 Volume 140, Page(s) 107810

Abstract: Mammalian heart cells and cells of leaves of Dionaea muscipula share the ability to generate propagated action potentials, because the excitable cells are electrically coupled. In the heart the propagated action potential causes synchronized contraction ... ...

Abstract	Mammalian heart cells and cells of leaves of Dionaea muscipula share the ability to generate propagated action potentials, because the excitable cells are electrically coupled. In the heart the propagated action potential causes synchronized contraction of the heart muscle after automatic generation of the impulse in the sinus node. In Dionaea propagation results in closure of the trap after activation of trigger hairs by an insect. The electrical activity can be recorded in the extracellular space as an extracellular electrogram, resulting from transmembrane currents. Although the underlying physiological mechanism that causes the electrogram is similar for heart and Dionaea cells, the contribution of the various ions to the transmembrane current is different. We recorded extracellular electrograms from Dionaea leaves and compared the recorded signals with those known from the heart. The morphology of the electrograms differed considerably. In comparison to activation in mammalian myocardium, electrograms of Dionaea are more temporally and spatially variable. Whereas electrograms in healthy myocardium recorded at some distance from the site of activation reveal a simple biphasic pattern, Dionaea activation showed positive, negative or biphasic deflections. Comparison of patch clamp data from plant cells and cardiomyocytes suggests a role of temperature and ion concentrations in extracellular space for the diversity of morphologies of the Dionaea electrograms.
MeSH term(s)	Droseraceae/cytology ; Droseraceae/physiology ; Electrophysiological Phenomena ; Extracellular Space/metabolism ; Heart/physiology
Language	English
Publishing date	2021-03-31
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article
ZDB-ID	2010650-6
ISSN	1878-562X ; 0302-4598 ; 1567-5394
ISSN (online)	1878-562X
ISSN	0302-4598 ; 1567-5394
DOI	10.1016/j.bioelechem.2021.107810
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Zs.A 1178: Show issues

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Article: Ex vivo

van der Waal, Jeanne G / Meijborg, Veronique M F / Belterman, Charly N W / Streekstra, Geert J / Oostendorp, Thom F / Coronel, Ruben

Frontiers in physiology

2021 Volume 12, Page(s) 737609

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2021-10-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2021.737609
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Article ; Online: Synchronization of repolarization by mechano-electrical coupling in the porcine heart.

Opthof, Tobias / Meijborg, Veronique M F / Belterman, Charly N W / Coronel, Ruben

Cardiovascular research

2015 Volume 108, Issue 1, Page(s) 181–187

Abstract: Aims: The aim of this study was to evaluate the effect of increase in left ventricular (LV) pressure on repolarization and activation-recovery intervals.: Methods and results: Six pig hearts were Langendorff-perfused. A compliant liquid-filled ... ...

Abstract	Aims: The aim of this study was to evaluate the effect of increase in left ventricular (LV) pressure on repolarization and activation-recovery intervals. Methods and results: Six pig hearts were Langendorff-perfused. A compliant liquid-filled balloon, connected with a pressure transducer, inserted through the mitral orifice, could be filled until the required LV systolic pressure was obtained. A grid of 121 electrodes (11 × 11; 5 mm interelectrode distance) was sutured on the LV free wall. Ventricular pacing at 600 ms and at 400 or 450 ms was either performed from the LV wall or from the ventricular septum. Under all these four conditions, the pressure wave occurred at the same moment relative to the onset of the QRS complex. Consequently, the time relation between local repolarization and the pressure wave differed between the various pacing sites. Repolarization times (RTs) at a cycle length (CL) of 600 ms were prolonged by increased pressure. With stimulation from the LV, when the pressure wave coincides with the action potentials (APs) late in their phase (sites with relatively early repolarization), an increase in pressure from 0 to 100 mmHg delayed repolarization more than with stimulation from the septum, when the pressure wave occurs at a relatively earlier phase of the AP (sites with relatively late repolarization). At pacing at CL 400/450 ms, an increase in pressure caused RT prolongation at the LV free wall during LV stimulation, but less RT prolongation or even shortening during septal stimulation. Conclusion: The effect of increased LV pressure is synchronization of repolarization.
MeSH term(s)	Action Potentials ; Animals ; Blood Pressure ; Cardiac Pacing, Artificial ; Electrocardiography ; Heart/physiology ; Male ; Swine ; Ventricular Function, Left
Language	English
Publishing date	2015-10-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80340-6
ISSN	1755-3245 ; 0008-6363
ISSN (online)	1755-3245
ISSN	0008-6363
DOI	10.1093/cvr/cvv140
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Zs.A 565: Show issues

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Article: Reduced Sodium Current in the Lateral Ventricular Wall Induces Inferolateral J-Waves.

Meijborg, Veronique M F / Potse, Mark / Conrath, Chantal E / Belterman, Charly N W / De Bakker, Jacques M T / Coronel, Ruben

Frontiers in physiology

2016 Volume 7, Page(s) 365

Abstract: Background: J-waves in inferolateral leads are associated with a higher risk for idiopathic ventricular fibrillation. We aimed to test potential mechanisms (depolarization or repolarization dependent) responsible for inferolateral J-waves. We ... ...

Abstract	Background: J-waves in inferolateral leads are associated with a higher risk for idiopathic ventricular fibrillation. We aimed to test potential mechanisms (depolarization or repolarization dependent) responsible for inferolateral J-waves. We hypothesized that inferolateral J-waves can be caused by regional delayed activation of myocardium that is activated late during normal conditions. Methods: Computer simulations were performed to evaluate how J-point elevation is influenced by reducing sodium current conductivity (GNa), increasing transient outward current conductivity (Gto), or cellular uncoupling in three predefined ventricular regions (lateral, anterior, or septal). Two pig hearts were Langendorff-perfused with selective perfusion with a sodium channel blocker of lateral or anterior/septal regions. Volume-conducted pseudo-electrocardiograms (ECG) were recorded to detect the presence of J-waves. Epicardial unipolar electrograms were simultaneously recorded to obtain activation times (AT). Results: Simulation data showed that conduction slowing, caused by reduced sodium current, in lateral, but not in other regions induced inferolateral J-waves. An increase in transient outward potassium current or cellular uncoupling in the lateral zone elicited slight J-point elevations which did not meet J-wave criteria. Additional conduction slowing in the entire heart attenuated J-waves and J-point elevations on the ECG, because of masking by the QRS. Experimental data confirmed that conduction slowing attributed to sodium channel blockade in the left lateral but not in the anterior/septal ventricular region induced inferolateral J-waves. J-waves coincided with the delayed activation. Conclusion: Reduced sodium current in the left lateral ventricular myocardium can cause inferolateral J-waves on the ECG.
Language	English
Publishing date	2016-08-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2016.00365
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Article ; Online: Sublingual microvascular perfusion is altered during normobaric and hyperbaric hyperoxia.

Milstein, Dan M J / Helmers, Renée / Hackmann, Sanne / Belterman, Charly N W / van Hulst, Robert A / de Lange, Jan

Microvascular research

2016 Volume 105, Page(s) 93–102

Abstract: Hyperoxia and hyperbaric oxygen therapy can restore oxygen tensions in tissues distressed by ischemic injury and poor vascularization and is believed to also yield angiogenesis and regulate tissue perfusion. The aim of this study was to develop a model ... ...

Abstract	Hyperoxia and hyperbaric oxygen therapy can restore oxygen tensions in tissues distressed by ischemic injury and poor vascularization and is believed to also yield angiogenesis and regulate tissue perfusion. The aim of this study was to develop a model in which hyperoxia-driven microvascular changes could be quantified and to test the hypothesis that microcirculatory responses to both normobaric (NB) and hyperbaric (HB) hyperoxic maneuvers are reversible. Sublingual mucosa microcirculation vessel density, proportion of perfused vessels, vessel diameters, microvascular flow index, macrohemodynamic, and blood gas parameters were examined in male rabbits breathing sequential O2/air mixtures of 21%, 55%, 100%, and return to 21% during NB (1.0 bar) and HB (2.5 bar) conditions. The results indicate that NB hyperoxia (55% and 100%) produced significant decreases in microvascular density and vascular diameters (p<0.01 and p<0.05, respectively) accompanied by significant increases in systolic and mean arterial blood pressure (p<0.05, respectively) with no changes in blood flow indices when compared to NB normoxia. HB normoxia/hyperoxia resulted in significant decreases in microvascular density (p<0.05), a transient rise in systolic blood pressure at 55% (p<0.01), and no changes in blood vessel diameter and blood flow indices when compared to NB hyperoxia. All microcirculation parameters reverted back to normal values upon return to NB normoxia. We conclude that NB/HB hyperoxia-driven changes elicit reversible physiological control of sublingual mucosa blood perfusion in the presence of steady cardiovascular function and that the absence of microvascular vasoconstriction during HB conditions suggests a beneficial mechanism associated with maintaining peak tissue perfusion states.
MeSH term(s)	Animals ; Blood Flow Velocity ; Disease Models, Animal ; Hyperbaric Oxygenation ; Hyperoxia/etiology ; Hyperoxia/physiopathology ; Male ; Microcirculation ; Microscopy, Video ; Microvessels/physiopathology ; Mouth Floor/blood supply ; Mouth Mucosa/blood supply ; Rabbits ; Regional Blood Flow ; Time Factors ; Vasoconstriction
Language	English
Publishing date	2016-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80307-8
ISSN	1095-9319 ; 0026-2862
ISSN (online)	1095-9319
ISSN	0026-2862
DOI	10.1016/j.mvr.2016.02.001
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Zs.A 746: Show issues

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Article ; Online: Noninvasive detection of spatiotemporal activation-repolarization interactions that prime idiopathic ventricular fibrillation.

Science translational medicine

2021 Volume 13, Issue 620, Page(s) eabi9317

Abstract: A comprehensive understanding of the interaction between triggers and electrical substrates leading to ventricular fibrillation (VF) and sudden cardiac arrest is lacking, and electrical substrates are difficult to detect and localize with current ... ...

Abstract	A comprehensive understanding of the interaction between triggers and electrical substrates leading to ventricular fibrillation (VF) and sudden cardiac arrest is lacking, and electrical substrates are difficult to detect and localize with current clinical tools. Here, we created repolarization time (RT) dispersion by regional drug infusion in perfused explanted human (
MeSH term(s)	Animals ; Electrocardiography/methods ; Heart Arrest ; Heart Ventricles ; Humans ; Swine ; Ventricular Fibrillation/diagnosis
Language	English
Publishing date	2021-11-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.abi9317
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Zs.A 6941: Show issues

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Article ; Online: Electrocardiographic T wave and its relation with ventricular repolarization along major anatomical axes.

Meijborg, Veronique M F / Conrath, Chantal E / Opthof, Tobias / Belterman, Charly N W / de Bakker, Jacques M T / Coronel, Ruben

Circulation. Arrhythmia and electrophysiology

2014 Volume 7, Issue 3, Page(s) 524–531

Abstract: Background: The genesis of the electrocardiographic T wave is incompletely understood and subject to controversy. We have correlated the ventricular repolarization sequence with simultaneously recorded T waves.: Methods and results: Nine pig hearts ... ...

Abstract	Background: The genesis of the electrocardiographic T wave is incompletely understood and subject to controversy. We have correlated the ventricular repolarization sequence with simultaneously recorded T waves. Methods and results: Nine pig hearts were Langendorff-perfused (atrial pacing, cycle length 650 ms). Local activation and repolarization times were derived from unipolar electrograms sampling the ventricular myocardium. Dispersion of repolarization time was determined along 4 anatomic axes: left ventricle (LV)-right ventricle (RV), LV:apico-basal, LV:anterior-posterior, and LV:transmural. The heart was immersed in a fluid-filled bucket containing 61 electrodes to determine Tp (Tpeak in lead of maximum integral), TpTe (Tp to Tend), and TpTe_total (first Tpeak in any lead to last Tend in any lead). Repolarization was nonlinearly distributed in time. RT25 (time at which 25% of sites were repolarized, 288±26 ms) concurred with Tp. TpTe was 38±8 ms, and TpTe_total was 75±9 ms. TpTe_total correlated with dispersion of repolarization time in the entire heart (73±18 ms), but not with dispersion of repolarization times along individual axes (LV-RV, 66±17 ms; LV:apico-basal, 51±18 ms; LV:anterior-posterior, 51±27 ms; mean LV:transmural, 14±7 ms; all n=9). Conclusions: We provide a correlation between local repolarization and T wave in a pseudo-ECG. Repolarization differences along all anatomic axes contribute to the T wave. TpTe_total represents total dispersion of repolarization. At Tp, ≈25% of ventricular sites have been repolarized.
MeSH term(s)	Action Potentials/physiology ; Animals ; Electrocardiography ; Electrodes, Implanted ; Electrophysiologic Techniques, Cardiac ; Heart/physiology ; Heart Conduction System/physiology ; Humans ; Male ; Models, Animal ; Reaction Time ; Sensitivity and Specificity ; Swine ; Ventricular Function/physiology
Language	English
Publishing date	2014-06
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2426129-4
ISSN	1941-3084 ; 1941-3149
ISSN (online)	1941-3084
ISSN	1941-3149
DOI	10.1161/CIRCEP.113.001622
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Zs.A 6667: Show issues

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Article ; Online: Experimental Validation of Noninvasive Epicardial and Endocardial Activation Imaging.

Oosterhoff, Peter / Meijborg, Veronique M F / van Dam, Peter M / van Dessel, Pascal F H M / Belterman, Charly N W / Streekstra, Geert J / de Bakker, Jacques M T / Coronel, Ruben / Oostendorp, Thom F

Circulation. Arrhythmia and electrophysiology

2016 Volume 9, Issue 8, Page(s) e004104

Abstract: Background: Noninvasive imaging of cardiac activation before ablation of the arrhythmogenic substrate can reduce electrophysiological procedure duration and help choosing between an endocardial or epicardial approach. A noninvasive imaging technique was ...

Abstract	Background: Noninvasive imaging of cardiac activation before ablation of the arrhythmogenic substrate can reduce electrophysiological procedure duration and help choosing between an endocardial or epicardial approach. A noninvasive imaging technique was evaluated that estimates both endocardial and epicardial activation from body surface potential maps. We performed a study in isolated and in situ pig hearts, estimating activation from body surface potential maps during sinus rhythm and localizing endocardial and epicardial stimulation sites. Methods and results: From 3 Langendorff-perfused pig hearts, 180 intramural unipolar electrograms were recorded during sinus rhythm and ectopic activation, together with pseudo-body surface potential map ECGs in 2 of them. From 4 other anesthetized pigs, 64-lead body surface potential maps were recorded during sinus rhythm and ventricular stimulation from 27 endocardial and epicardial sites. The ventricular activation pattern was computed from the recorded QRS complexes. For both Langendorff-perfused hearts, the calculated epicardial and endocardial activation patterns showed good qualitative correspondence to the patterns obtained with needle electrodes. Absolute timing difference for sinus rhythm was 10±5 and 11±8 ms respectively, and for ectopic activation 6±5 and 7±6 ms, respectively. Calculated activation for the in situ hearts in sinus rhythm was similar to patterns recorded in Langendorff-perfused hearts. During stimulation, the distance between the stimulation site and calculated site of earliest activation was 18 (15-27) mm, and 23 of 27 stimulation sites were correctly mapped to either endocardium or epicardium. Conclusions: Noninvasive activation imaging is able to determine earliest ventricular activation and discriminate endocardial from epicardial origin of activation with clinically relevant accuracy.
MeSH term(s)	Animals ; Body Surface Potential Mapping ; Cardiac Catheterization ; Electrocardiography ; Endocardium/physiology ; Fluoroscopy ; Heart Conduction System/physiology ; Imaging, Three-Dimensional ; Pericardium/physiology ; Swine ; Tomography, X-Ray Computed
Language	English
Publishing date	2016-08-24
Publishing country	United States
Document type	Journal Article ; Validation Studies ; Research Support, Non-U.S. Gov't
ZDB-ID	2426129-4
ISSN	1941-3084 ; 1941-3149
ISSN (online)	1941-3084
ISSN	1941-3149
DOI	10.1161/CIRCEP.116.004104
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Article ; Online: Neurokinin-3 receptor activation selectively prolongs atrial refractoriness by inhibition of a background K

Veldkamp, Marieke W / Geuzebroek, Guillaume S C / Baartscheer, Antonius / Verkerk, Arie O / Schumacher, Cees A / Suarez, Gedeon G / Berger, Wouter R / Casini, Simona / van Amersfoorth, Shirley C M / Scholman, Koen T / Driessen, Antoine H G / Belterman, Charly N W / van Ginneken, Antoni C G / de Groot, Joris R / de Bakker, Jacques M T / Remme, Carol Ann / Boukens, Bas J / Coronel, Ruben

Nature communications

2018 Volume 9, Issue 1, Page(s) 4357

Abstract: The cardiac autonomic nervous system (ANS) controls normal atrial electrical function. The cardiac ANS produces various neuropeptides, among which the neurokinins, whose actions on atrial electrophysiology are largely unknown. We here demonstrate that ... ...

Abstract	The cardiac autonomic nervous system (ANS) controls normal atrial electrical function. The cardiac ANS produces various neuropeptides, among which the neurokinins, whose actions on atrial electrophysiology are largely unknown. We here demonstrate that the neurokinin substance-P (Sub-P) activates a neurokinin-3 receptor (NK-3R) in rabbit, prolonging action potential (AP) duration through inhibition of a background potassium current. In contrast, ventricular AP duration was unaffected by NK-3R activation. NK-3R stimulation lengthened atrial repolarization in intact rabbit hearts and consequently suppressed arrhythmia duration and occurrence in a rabbit isolated heart model of atrial fibrillation (AF). In human atrial appendages, the phenomenon of NK-3R mediated lengthening of atrial repolarization was also observed. Our findings thus uncover a pathway to selectively modulate atrial AP duration by activation of a hitherto unidentified neurokinin-3 receptor in the membrane of atrial myocytes. NK-3R stimulation may therefore represent an anti-arrhythmic concept to suppress re-entry-based atrial tachyarrhythmias, including AF.
MeSH term(s)	Action Potentials ; Animals ; Arrhythmias, Cardiac ; Atrial Fibrillation ; Atrial Function ; Heart Atria/metabolism ; Humans ; Potassium Channel Blockers ; Potassium Channels/metabolism ; Rabbits ; Receptors, Neurokinin-3/metabolism ; Receptors, Neurokinin-3/physiology
Chemical Substances	Potassium Channel Blockers ; Potassium Channels ; Receptors, Neurokinin-3
Language	English
Publishing date	2018-10-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2041-1723
ISSN (online)	2041-1723
DOI	10.1038/s41467-018-06530-5
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Article ; Online: A diet rich in unsaturated fatty acids prevents progression toward heart failure in a rabbit model of pressure and volume overload.

Den Ruijter, Hester M / Verkerk, Arie O / Schumacher, Cees A / Houten, Sander M / Belterman, Charly N W / Baartscheer, Antonius / Brouwer, Ingeborg A / van Bilsen, Marc / de Roos, Baukje / Coronel, Ruben

Circulation. Heart failure

2012 Volume 5, Issue 3, Page(s) 376–384

Abstract: Background: During heart failure (HF), cardiac metabolic substrate preference changes from fatty acid (FA) toward glucose oxidation. This change may cause progression toward heart failure. We hypothesize that a diet rich in FAs may prevent this process, ...

Abstract	Background: During heart failure (HF), cardiac metabolic substrate preference changes from fatty acid (FA) toward glucose oxidation. This change may cause progression toward heart failure. We hypothesize that a diet rich in FAs may prevent this process, and that dietary ω3-FAs have an added antiarrhythmic effect based on action potential (AP) shortening in animals with HF. Methods and results: Rabbits were fed a diet containing 1.25% (w/w) high oleic sunflower oil (HF-ω9, N=11), 1.25% fish oil (HF-ω3, N=11), or no supplement (HF-control, N=8). Subsequently, HF was induced by volume and pressure overload. After 4 months, HF-parameters were assessed, electrocardiograms were recorded, and blood and ventricular tissue were collected. Myocytes were isolated for patch clamp or intracellular Ca(2+)- recordings to study electrophysiologic remodeling and arrhythmogenesis. Both the HF-ω9 and the HF-ω3 groups had larger myocardial FA oxidation capacity than HF control. The HF-ω3 group had significantly lower mean (± SEM) relative heart and lung weight (3.3±0.13 and 3.2±0.12 g kg(-1), respectively) than HF control (4.8±0.30 and 4.5±0.23), and shorter QTc intervals (167±2.6 versus 182±6.4). The HF-ω9 also displayed a significantly reduced relative heart weight (3.6±0.26), but had similar QTc (179±4.3) compared with HF control. AP duration in the HF-ω3 group was ≈20% shorter due to increased I(to1) and I(K1) and triggered activity, and Ca(2+)-aftertransients were less than in the HF-ω9 group. Conclusions: Dietary unsaturated FAs started prior to induction of HF prevent hypertrophy and HF. In addition, fish oil FAs prevent HF-induced electrophysiologic remodeling and arrhythmias.
MeSH term(s)	Action Potentials/physiology ; Administration, Oral ; Animals ; Arrhythmias, Cardiac/pathology ; Arrhythmias, Cardiac/physiopathology ; Arrhythmias, Cardiac/prevention & control ; Calcium/metabolism ; Cardiomegaly/pathology ; Cardiomegaly/physiopathology ; Cardiomegaly/prevention & control ; Dietary Fats, Unsaturated/administration & dosage ; Dietary Fats, Unsaturated/therapeutic use ; Electrocardiography ; Electrophysiologic Techniques, Cardiac ; Fatty Acids, Unsaturated/administration & dosage ; Fatty Acids, Unsaturated/therapeutic use ; Heart Failure/pathology ; Heart Failure/physiopathology ; Heart Failure/prevention & control ; Male ; Models, Animal ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; Patch-Clamp Techniques ; Rabbits
Chemical Substances	Dietary Fats, Unsaturated ; Fatty Acids, Unsaturated ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2012-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429459-7
ISSN	1941-3297 ; 1941-3289
ISSN (online)	1941-3297
ISSN	1941-3289
DOI	10.1161/CIRCHEARTFAILURE.111.963116
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