Bengel, Philipp

[["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Stehle, Thea"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Knierim, Maria"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Holzamer, Andreas"],["dc.contributor.author","Hilker, Michael"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2020-12-10T14:10:25Z"],["dc.date.available","2020-12-10T14:10:25Z"],["dc.date.issued","2020"],["dc.description.abstract","Pharmacologic approaches for the treatment of atrial arrhythmias are limited due to side effects and low efficacy. Thus, the identification of new antiarrhythmic targets is of clinical interest. Recent genome studies suggested an involvement of SCN10A sodium channels (NaV1.8) in atrial electrophysiology. This study investigated the role and involvement of NaV1.8 (SCN10A) in arrhythmia generation in the human atria and in mice lacking NaV1.8. NaV1.8 mRNA and protein were detected in human atrial myocardium at a significant higher level compared to ventricular myocardium. Expression of NaV1.8 and NaV1.5 did not differ between myocardium from patients with atrial fibrillation and sinus rhythm. To determine the electrophysiological role of NaV1.8, we investigated isolated human atrial cardiomyocytes from patients with sinus rhythm stimulated with isoproterenol. Inhibition of NaV1.8 by A-803467 or PF-01247324 showed no effects on the human atrial action potential. However, we found that NaV1.8 significantly contributes to late Na+ current and consequently to an increased proarrhythmogenic diastolic sarcoplasmic reticulum Ca2+ leak in human atrial cardiomyocytes. Selective pharmacological inhibition of NaV1.8 potently reduced late Na+ current, proarrhythmic diastolic Ca2+ release, delayed afterdepolarizations as well as spontaneous action potentials. These findings could be confirmed in murine atrial cardiomyocytes from wild-type mice and also compared to SCN10A−/− mice (genetic ablation of NaV1.8). Pharmacological NaV1.8 inhibition showed no effects in SCN10A−/− mice. Importantly, in vivo experiments in SCN10A−/− mice showed that genetic ablation of NaV1.8 protects against atrial fibrillation induction. This study demonstrates that NaV1.8 is expressed in the murine and human atria and contributes to late Na+ current generation and cellular arrhythmogenesis. Blocking NaV1.8 selectively counteracts this pathomechanism and protects against atrial arrhythmias. Thus, our translational study reveals a new selective therapeutic target for treating atrial arrhythmias."],["dc.identifier.doi","10.1007/s00395-020-0780-8"],["dc.identifier.pmid","32078054"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70756"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/349"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.rights","CC BY 4.0"],["dc.title","Inhibition of NaV1.8 prevents atrial arrhythmogenesis in human and mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","179"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Current Heart Failure Reports"],["dc.bibliographiccitation.lastpage","186"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2019-01-30T13:29:01Z"],["dc.date.available","2019-01-30T13:29:01Z"],["dc.date.issued","2017"],["dc.description.abstract","Over the last years, evidence is accumulating that enhanced late sodium current (INaL) in cardiac pathologies has fundamental consequences for cellular electrophysiology. This review discusses the underlying mechanisms of INaL-induced arrhythmias and the significance of INaL-inhibition as a possible therapeutic approach."],["dc.identifier.doi","10.1007/s11897-017-0333-0"],["dc.identifier.pmid","28455610"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57422"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1546-9549"],["dc.title","Inhibition of Late Sodium Current as an Innovative Antiarrhythmic Strategy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Pacing and Clinical Electrophysiology"],["dc.contributor.author","Schlögl, Simon"],["dc.contributor.author","Schlögl, Klaudia Stella"],["dc.contributor.author","Haarmann, Helge"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Bergau, Leonard"],["dc.contributor.author","Rasenack, Eva"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Zabel, Markus"],["dc.date.accessioned","2021-12-01T09:21:15Z"],["dc.date.available","2021-12-01T09:21:15Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1111/pace.14392"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94387"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","1540-8159"],["dc.relation.issn","0147-8389"],["dc.title","Remote magnetic navigation versus manual catheter ablation of atrial fibrillation: A single center long‐term comparison"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","6586"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Hartmann, Nico Horst"],["dc.contributor.author","A. Mohamed, Belal"],["dc.contributor.author","Krekeler, Miriam Celine"],["dc.contributor.author","Maurer, Wiebke"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Trum, Maximilian"],["dc.contributor.author","Sossalla, Samuel Tobias"],["dc.date.accessioned","2021-12-01T09:20:52Z"],["dc.date.available","2021-12-01T09:20:52Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract An interplay between Ca 2+ /calmodulin-dependent protein kinase IIδc (CaMKIIδc) and late Na + current (I NaL ) is known to induce arrhythmias in the failing heart. Here, we elucidate the role of the sodium channel isoform Na V 1.8 for CaMKIIδc-dependent proarrhythmia. In a CRISPR-Cas9-generated human iPSC-cardiomyocyte homozygous knock-out of Na V 1.8, we demonstrate that Na V 1.8 contributes to I NaL formation. In addition, we reveal a direct interaction between Na V 1.8 and CaMKIIδc in cardiomyocytes isolated from patients with heart failure (HF). Using specific blockers of Na V 1.8 and CaMKIIδc, we show that Na V 1.8-driven I NaL is CaMKIIδc-dependent and that Na V 1.8-inhibtion reduces diastolic SR-Ca 2+ leak in human failing cardiomyocytes. Moreover, increased mortality of CaMKIIδc-overexpressing HF mice is reduced when a Na V 1.8 knock-out is introduced. Cellular and in vivo experiments reveal reduced ventricular arrhythmias without changes in HF progression. Our work therefore identifies a proarrhythmic CaMKIIδc downstream target which may constitute a prognostic and antiarrhythmic strategy."],["dc.identifier.doi","10.1038/s41467-021-26690-1"],["dc.identifier.pii","26690"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94290"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/412"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.eissn","2041-1723"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 4.0"],["dc.title","Detrimental proarrhythmogenic interaction of Ca2+/calmodulin-dependent protein kinase II and NaV1.8 in heart failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1690"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","1700"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Bollenberg, Hannah"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Kovács, Árpád"],["dc.contributor.author","Schach, Christian"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Renner, André"],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","Fischer, Thomas"],["dc.contributor.author","Van Linthout, Sophie"],["dc.contributor.author","Tschöpe, Carsten"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hamdani, Nazha"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2019-02-19T13:12:22Z"],["dc.date.available","2019-02-19T13:12:22Z"],["dc.date.issued","2018"],["dc.description.abstract","Aims Empagliflozin, a clinically used oral antidiabetic drug that inhibits the sodium-dependent glucose co-transporter 2, has recently been evaluated for its cardiovascular safety. Surprisingly, empagliflozin reduced mortality and hospitalization for heart failure (HF) compared to placebo. However, the underlying mechanisms remain unclear. Therefore, our study aims to investigate whether empagliflozin may cause direct pleiotropic effects on the myocardium. Methods and results In order to assess possible direct myocardial effects of empagliflozin, we performed contractility experiments with in toto-isolated human systolic end-stage HF ventricular trabeculae. Empagliflozin significantly reduced diastolic tension, whereas systolic force was not changed. These results were confirmed in murine myocardium from diabetic and non-diabetic mice, suggesting independent effects from diabetic conditions. In human HF cardiomyocytes, empagliflozin did not influence calcium transient amplitude or diastolic calcium level. The mechanisms underlying the improved diastolic function were further elucidated by studying myocardial fibres from patients and rats with diastolic HF (HF with preserved ejection fraction, HFpEF). Empagliflozin beneficially reduced myofilament passive stiffness by enhancing phosphorylation levels of myofilament regulatory proteins. Intravenous injection of empagliflozin in anaesthetized HFpEF rats significantly improved diastolic function measured by echocardiography, while systolic contractility was unaffected. Conclusion Empagliflozin causes direct pleiotropic effects on the myocardium by improving diastolic stiffness and hence diastolic function. These effects were independent of diabetic conditions. Since pharmacological therapy of diastolic dysfunction and HF is an unmet need, our results provide a rationale for new translational studies and might also contribute to the understanding of the EMPA-REG OUTCOME trial."],["dc.identifier.doi","10.1002/ejhf.1328"],["dc.identifier.pmid","30328645"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57583"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/239"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A11: Absolute Arrhythmie bei Vorhofflimmern - ein neuer Mechanismus, der zu einer Störung von Ca2+-Homöostase und elektrischer Stabilität in der Transition zur Herzinsuffizienz führt"],["dc.relation.issn","1879-0844"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG T. Fischer"],["dc.title","Empagliflozin directly improves diastolic function in human heart failure"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Journal of Interventional Cardiac Electrophysiology"],["dc.contributor.author","Schlögl, Simon"],["dc.contributor.author","Schlögl, Klaudia Stella"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Bergau, Leonard"],["dc.contributor.author","Haarmann, Helge"],["dc.contributor.author","Rasenack, Eva"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Zabel, Markus"],["dc.date.accessioned","2022-09-01T09:49:21Z"],["dc.date.available","2022-09-01T09:49:21Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n \n Background\n In atrial fibrillation (AF) patients, catheter ablation of pulmonary veins (PVI) is the most effective therapeutic option to maintain sinus rhythm. To improve successful PVI, contact force–sensing (CF) catheters became routinely available. Previous studies did not clearly show superior clinical efficacy in comparison with non-CF catheters.\n \n \n Methods\n We investigated consecutive patients, who underwent index PVI for AF at our hospital between 2012 and 2018. Three hundred and fifty-four patients were ablated without CF. After availability of CF catheters in 2016, 317 patients were ablated using CF. In case of crossover between the groups, follow-up was censored. The primary endpoint was any documented atrial tachycardia (AT) or atrial fibrillation > 30 s after a 3-month blanking period. Secondary endpoints were procedural characteristics and periprocedural complications.\n \n \n Results\n \n There was no significant difference between the groups at baseline except hyperlipidemia. After 365 days of follow-up, 67% of patients in the CF group remained free from AF/AT recurrence compared to 59% in non-CF group (\n P\n  = 0.038). In multivariable Cox regression analysis, non-CF ablation was an independent risk factor for AF recurrence besides age and persistent AF. Total fluoroscopy time (15 ± 7.6 vs. 28 ± 15.9 min) and total procedure time (114 ± 29.6 vs. 136 ± 38.5 min) were significantly lower for CF-guided PVI (\n P\n  < 0.001). Complication rates did not differ between groups (\n P\n  = 0.661).\n \n \n \n Conclusions\n In our study, the AT/AF recurrence rate and pulmonary vein reconnection rate is lower after CF PVI with a similar complication rate but lower total procedure time and total fluoroscopy time compared to non-CF PVI."],["dc.identifier.doi","10.1007/s10840-022-01316-8"],["dc.identifier.pii","1316"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113401"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","1572-8595"],["dc.relation.issn","1383-875X"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Impact of open-irrigated radiofrequency catheter with contact force measurement on the efficacy and safety of atrial fibrillation ablation: a single-center direct comparison"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Respiration"],["dc.bibliographiccitation.lastpage","13"],["dc.contributor.author","Spiesshoefer, Jens"],["dc.contributor.author","Henke, Carolin"],["dc.contributor.author","Kabitz, Hans Joachim"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Schütt, Katharina"],["dc.contributor.author","Nofer, Jerzy-Roch"],["dc.contributor.author","Spieker, Maximilian"],["dc.contributor.author","Orwat, Stefan"],["dc.contributor.author","Diller, Gerhard Paul"],["dc.contributor.author","Strecker, Jan Kolia"],["dc.contributor.author","Giannoni, Alberto"],["dc.contributor.author","Dreher, Michael"],["dc.contributor.author","Randerath, Winfried Johannes"],["dc.contributor.author","Boentert, Matthias"],["dc.contributor.author","Tuleta, Izabela"],["dc.date.accessioned","2021-04-14T08:31:23Z"],["dc.date.available","2021-04-14T08:31:23Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1159/000509940"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83580"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1423-0356"],["dc.relation.issn","0025-7931"],["dc.title","Heart Failure Results in Inspiratory Muscle Dysfunction Irrespective of Left Ventricular Ejection Fraction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1"],["dc.bibliographiccitation.firstpage","2"],["dc.bibliographiccitation.journal","European Heart Journal - Case Reports"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Zabel, Markus"],["dc.contributor.author","Lüthje, Lars"],["dc.date.accessioned","2020-10-08T10:54:49Z"],["dc.date.accessioned","2021-10-27T13:22:20Z"],["dc.date.available","2020-10-08T10:54:49Z"],["dc.date.available","2021-10-27T13:22:20Z"],["dc.date.issued","2020"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2020"],["dc.identifier.doi","10.1093/ehjcr/ytaa244"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17588"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92086"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","2514-2119"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Pulmonary vein ablation in a patient with a large left common pulmonary vein joining a large right common trunk"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","45"],["dc.bibliographiccitation.journal","International Journal of Cardiology"],["dc.bibliographiccitation.lastpage","51"],["dc.bibliographiccitation.volume","318"],["dc.contributor.author","Spiesshoefer, Jens"],["dc.contributor.author","Orwat, Stefan"],["dc.contributor.author","Henke, Carolin"],["dc.contributor.author","Kabitz, Hans-Joachim"],["dc.contributor.author","Katsianos, Stratis"],["dc.contributor.author","Borrelli, Chiara"],["dc.contributor.author","Baumgartner, Helmut"],["dc.contributor.author","Nofer, Jerzy-Roch"],["dc.contributor.author","Spieker, Maximilian"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Giannoni, Alberto"],["dc.contributor.author","Dreher, Michael"],["dc.contributor.author","Boentert, Matthias"],["dc.contributor.author","Diller, Gerhard Paul"],["dc.date.accessioned","2021-04-14T08:32:02Z"],["dc.date.available","2021-04-14T08:32:02Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.ijcard.2020.06.055"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83784"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.issn","0167-5273"],["dc.title","Inspiratory muscle dysfunction and restrictive lung function impairment in congenital heart disease: Association with immune inflammatory response and exercise intolerance"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","35"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","46"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Trum, Maximilian"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2021-04-14T08:25:53Z"],["dc.date.available","2021-04-14T08:25:53Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.yjmcc.2020.05.002"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81759"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.issn","0022-2828"],["dc.title","Contribution of the neuronal sodium channel NaV1.8 to sodium- and calcium-dependent cellular proarrhythmia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]