Sossalla, Samuel Tobias

[["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","642"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","ESC Heart Failure"],["dc.bibliographiccitation.lastpage","648"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Wagemann, Olivia"],["dc.contributor.author","Lücht, Charlotte M."],["dc.contributor.author","Trum, Maximilian"],["dc.contributor.author","Hammer, Karin P."],["dc.contributor.author","Sag, Can Martin"],["dc.contributor.author","Lebek, Simon"],["dc.contributor.author","Tarnowski, Daniel"],["dc.contributor.author","Reinders, Jörg"],["dc.contributor.author","Perbellini, Filippo"],["dc.contributor.author","Terracciano, Cesare"],["dc.contributor.author","Schmid, Christof"],["dc.contributor.author","Schopka, Simon"],["dc.contributor.author","Hilker, Michael"],["dc.contributor.author","Zausig, York"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Sossalla, Samuel T."],["dc.contributor.author","Schweda, Frank"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Wagner, Stefan"],["dc.date.accessioned","2020-12-10T14:06:09Z"],["dc.date.available","2020-12-10T14:06:09Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1002/ehf2.12336"],["dc.identifier.issn","2055-5822"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69797"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Empagliflozin reduces Ca/calmodulin-dependent kinase II activity in isolated ventricular cardiomyocytes"],["dc.title.alternative","Empagliflozin reduces CaMKII activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1262"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","1274"],["dc.bibliographiccitation.volume","123"],["dc.contributor.author","Luo, Min"],["dc.contributor.author","Guan, Xiaoqun"],["dc.contributor.author","Luczak, Elizabeth D."],["dc.contributor.author","Lang, Di"],["dc.contributor.author","Kutschke, William"],["dc.contributor.author","Gao, Zhan"],["dc.contributor.author","Yang, Jinying"],["dc.contributor.author","Glynn, Patric"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Swaminathan, Paari D."],["dc.contributor.author","Weiss, Robert M."],["dc.contributor.author","Yang, Baoli"],["dc.contributor.author","Rokita, Adam G."],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Efimov, Igor R."],["dc.contributor.author","Hund, Thomas J."],["dc.contributor.author","Anderson, Mark E."],["dc.date.accessioned","2018-11-07T09:27:39Z"],["dc.date.available","2018-11-07T09:27:39Z"],["dc.date.issued","2013"],["dc.description.abstract","Diabetes increases oxidant stress and doubles the risk of dying after myocardial infarction, but the mechanisms underlying increased mortality are unknown. Mice with streptozotocin-induced diabetes developed profound heart rate slowing and doubled mortality compared with controls after myocardial infarction. Oxidized Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) was significantly increased in pacemaker tissues from diabetic patients compared with that in nondiabetic patients after myocardial infarction. Streptozotocin-treated mice had increased pacemaker cell ox-CaMKII and apoptosis, which were further enhanced by myocardial infarction. We developed a knockin mouse model of oxidation-resistant CaMKII delta (MM-VV), the isoform associated with cardiovascular disease. Streptozotocin-treated MM-VV mice and WT mice infused with MitoTEMPO, a mitochondrial targeted antioxidant, expressed significantly less ox-CaMKII, exhibited increased pacemaker cell survival, maintained normal heart rates, and were resistant to diabetes-attributable mortality after myocardial infarction. Our findings suggest that activation of a mitochondrial/ox-CaMKII pathway contributes to increased sudden death in diabetic patients after myocardial infarction."],["dc.identifier.doi","10.1172/JCI65268"],["dc.identifier.isi","000315749400036"],["dc.identifier.pmid","23426181"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30588"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/105"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A03: Bedeutung CaMKII-abhängiger Mechanismen für die Arrhythmogenese bei Herzinsuffizienz"],["dc.relation.issn","0021-9738"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.title","Diabetes increases mortality after myocardial infarction by oxidizing CaMKII"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","673"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","680"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Schillinger, Wolfgang"],["dc.contributor.author","Teucher, Nils"],["dc.contributor.author","Christians, Claus"],["dc.contributor.author","Kohlhaas, Michael"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Van Nguyen, Phuc"],["dc.contributor.author","Schmidt, Albrecht G."],["dc.contributor.author","Schunck, Ortwin"],["dc.contributor.author","Nebendahl, Klaus"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Zeitz, Oliver"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.date.accessioned","2017-09-07T11:52:27Z"],["dc.date.available","2017-09-07T11:52:27Z"],["dc.date.issued","2006"],["dc.description.abstract","We investigated the hypothesis that increased intracellular [Na+](i) in heart failure contributes to preservation of SR Ca2+ load which may become particularly evident at slow heart rates. [Na+]i in SBFI-loaded myocytes from rabbits with pacing-induced heart failure (PHF) was significantly higher at each frequency as compared to Sham-operated animals. Furthermore, PHF rabbits demonstrated reduced SR Ca2+-ATPase protein levels (-37%, p < 0.04) but unchanged Na+/Ca2+ exchanger protein levels. At 0.25 Hz, isometric force was similar in cardiac trabeculae from PHF rabbits as compared to control (PHF, 3.6 +/- 1.3; Sham, 4.4 +/- 0.6 mN/mm(2)). Rapid cooling contractures (RCCs) were unchanged indicating preserved SR Ca2+ load at this frequency. In Sham, isometric twitch force increased with rising frequencies to 29.0 +/- 2.8 mN/mm(2) at 3.0 Hz (p < 0.05) as compared to 0.25 Hz. RCCs showed a parallel increase by 186 +/- 47% (p < 0.01). In PHF, frequency-dependent increase in force (15.8 +/- 4.7 mN/mm(2) at 3.0 Hz) and RCCs (increase by 70 +/- 40%) were significantly blunted. Thus, in PHF in rabbits SR Ca2+ load is preserved at low frequencies despite decreased SR Ca2+-ATPase expression. This may result from [Na+](i)-dependent changes in Na+/Ca2+ exchanger activity. (c) 2006 European Society of Cardiology. Published by Elsevier B.V All rights reserved."],["dc.identifier.doi","10.1016/j.ejheart.2006.01.013"],["dc.identifier.gro","3143598"],["dc.identifier.isi","000242383300002"],["dc.identifier.pmid","16540370"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1130"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1388-9842"],["dc.title","High intracellular Na+ preserves myocardial function at low heart rates in isolated myocardium from failing hearts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","32"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","43"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Rasenack, Eva C. L."],["dc.contributor.author","Ruff, Hanna"],["dc.contributor.author","Weber, Sarah L."],["dc.contributor.author","Schoendube, Friedrich A."],["dc.contributor.author","Tirilomis, Theodor"],["dc.contributor.author","Tenderich, Gero"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Belardinelli, Luiz"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:48:16Z"],["dc.date.available","2017-09-07T11:48:16Z"],["dc.date.issued","2008"],["dc.description.abstract","The goal of this study was to test the hypothesis that the novel anti-ischemic drug ratiolazine, which is known to inhibit late I-Na, could reduce intracellular [Na+](i) and diastolic [Ca2+](i) overload and improve diastolic function. Contractile dysfunction in human heart failure (HF) is associated with increased [Na+](i) and elevated diastolic [Ca2+](i). Increased Na influx through voltage-gated Na+ channels (late I-Na) has been suggested to contribute to elevated [Na+](i) in HF. In isometrically contracting ventricular muscle strips from end-stage failing human hearts, ranolazine (10 mu mol/L) did not exert negative inotropic effects on twitch force amplitude. However, ranolazine significantly reduced frequency-dependent increase in diastolic tension (i.e., diastolic dysfunction) by similar to 30% without significantly affecting sarcoplasmic reticulum (SR) Ca2+ loading. To investigate the mechanism of action of this beneficial effect of ranolazine on diastolic tension, Anemonia sulcata toxin II (ATX-II, 40 nmol/L) was used to increase intracellular Na+ loading in ventricular rabbit myocytes. ATX-II caused a significant rise in [Na+](i) typically seen in heart failure via increased late I-Na. In parallel, ATX-II significantly increased diastolic [Ca2+](i). In the presence of ranolazine the increases in late I-Na, as well as [Na+](i) and diastolic [Ca2+](i) were significantly blunted at all stimulation rates without significantly decreasing Ca2+ transient amplitudes or SR Ca2+ content. In summary, ranolazine reduced the frequency dependent increase in diastolic tension without having negative inotropic effects on contractility of muscles from end-stage failing human hearts. Moreover, in rabbit myocytes the increases in late I-Na, [Na+](i) and [Ca2+](i) caused by ATX-II, were significantly blunted by ranolazine. These results suggest that ratiolazine may be of therapeutic benefit in conditions of diastolic dysfunction due to elevated [Na+](i) and diastolic [Ca2+](i). (C) 2008 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.yjmcc.2008.03.006"],["dc.identifier.gro","3143272"],["dc.identifier.isi","000257543800004"],["dc.identifier.pmid","18439620"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/767"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Ltd- Elsevier Science Ltd"],["dc.relation.eissn","1095-8584"],["dc.relation.issn","0022-2828"],["dc.title","Ranolazine improves diastolic dysfunction in isolated myocardium from failing human hearts - Role of late sodium current and intracellular ion accumulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.volume","87"],["dc.contributor.author","Fluschnik, Nina"],["dc.contributor.author","Sossalla, Samuel T."],["dc.contributor.author","Ort, Katharina R."],["dc.contributor.author","Neef, S."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars. S."],["dc.date.accessioned","2018-11-07T08:41:33Z"],["dc.date.available","2018-11-07T08:41:33Z"],["dc.date.issued","2010"],["dc.format.extent","S93"],["dc.identifier.isi","000282114100226"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19494"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.eventlocation","Berlin, GERMANY"],["dc.relation.issn","0008-6363"],["dc.title","Beneficial effects of CaMKII inhibition in the human failing heart"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1111"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Europace"],["dc.bibliographiccitation.lastpage","1118"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Stehle, Thea"],["dc.contributor.author","Lebek, Simon"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Keyser, Andreas"],["dc.contributor.author","Rupprecht, Leopold"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Maier, Lars S"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2021-04-14T08:24:15Z"],["dc.date.available","2021-04-14T08:24:15Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1093/europace/euaa079"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81221"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1532-2092"],["dc.relation.issn","1099-5129"],["dc.title","Dantrolene reduces CaMKIIδC-mediated atrial arrhythmias"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","95"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","106"],["dc.bibliographiccitation.volume","94"],["dc.contributor.author","Hartmann, Nico H."],["dc.contributor.author","Mason, Fleur E."],["dc.contributor.author","Braun, Inga"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Voigt, Niels"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Dobrev, Dobromir"],["dc.contributor.author","Danner, Bernhard C."],["dc.contributor.author","Renner, André"],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","Belardinelli, Luiz"],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2017-09-07T11:44:54Z"],["dc.date.available","2017-09-07T11:44:54Z"],["dc.date.issued","2016"],["dc.description.abstract","Introduction: Pharmacological rhythm control of atrial fibrillation (AF) in patients with structural heart disease is limited. Ranolazine in combination with low dose dronedarone remarkably reduced AF-burden in the phase II HARMONY trial. We thus aimed to investigate the possible mechanisms underlying these results. Methods and results: Patch clamp experiments revealed that ranolazine (5 mu M), low-dose dronedarone (0.3 mu M), and the combination significantly prolonged action potential duration (APD(90)) in atrial myocytes from patients in sinus rhythm (prolongation by 23.5 +/- 0.1%, 31.7 +/- 0.1% and 25.6 +/- 0.1% respectively). Most importantly, in atrial myocytes from patients with AF ranolazine alone, but more the combination with dronedarone, also prolonged the typically abbreviated APD(90) (prolongation by 21.6 +/- 0.1% and 31.9 +/- 0.1% respectively). It was clearly observed that neither ranolazine, dronedarone nor the combination significantly changed the APD or contractility and twitch force in ventricular myocytes or trabeculae from patients with heart failure (HF). Interestingly ranolazine, and more so the combination, but not dronedarone alone, caused hyperpolarization of the resting membrane potential in cardiomyocytes from AF. As measured by confocal microscopy (Fluo-3), ranolazine, dronedarone and the combination significantly suppressed diastolic sarcoplasmic reticulum (SR) Ca2+ leak in myocytes from sinus rhythm (reduction by ranolazine: 89.0 +/- 30.7%, dronedarone: 75.6 +/- 27.4% and combination: 78.0 +/- 272%), in myocytes from AF (reduction by ranolazine: 67.6 +/- 33.7%, dronedarone: 86.5 +/- 31.7% and combination: 81.0 +/- 33.3%), as well as in myocytes from HF (reduction by ranolazine: 64.8 +/- 26.5% and dronedarone: 65.9 +/- 29.3%). Conclusions: Electrophysiological measurements during exposure to ranolazine alone or in combination with low-dose dronedarone showed APD prolongation, cellular hyperpolarization and reduced SR Ca2+ leak in human atrial myocytes. The combined inhibitory effects on various currents, in particular Na+ and K+ currents, may explain the anti-AF effects observed in the HARMONY trial. Therefore, the combination of ranolazine and dronedarone, but also ranolazine alone, may be promising new treatment options for AF, especially in patients with HF, and merit further clinical investigation. (C) 2016 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.yjmcc.2016.03.012"],["dc.identifier.gro","3141690"],["dc.identifier.isi","000376839000011"],["dc.identifier.pmid","27056421"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8938"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/146"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["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","1095-8584"],["dc.relation.issn","0022-2828"],["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.relation.workinggroup","RG Voigt (Molecular Pharmacology)"],["dc.title","The combined effects of ranolazine and dronedarone on human atrial and ventricular electrophysiology"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1150"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Circulation Research"],["dc.bibliographiccitation.lastpage","U215"],["dc.bibliographiccitation.volume","107"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Fluschnik, Nina"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Ort, Katharina R."],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Schulte, Timo"],["dc.contributor.author","Wittkoepper, Katrin"],["dc.contributor.author","Renner, André"],["dc.contributor.author","Schmitto, Jan D."],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:45:15Z"],["dc.date.available","2017-09-07T11:45:15Z"],["dc.date.issued","2010"],["dc.description.abstract","Rationale: Heart failure (HF) is known to be associated with increased Ca2+/calmodulin-dependent protein kinase (CaMK)II expression and activity. There is still controversial discussion about the functional role of CaMKII in HF. Moreover, CaMKII inhibition has never been investigated in human myocardium. Objective: We sought to investigate detailed CaMKII delta expression in end-stage failing human hearts (dilated and ischemic cardiomyopathy) and the functional effects of CaMKII inhibition on contractility. Methods and Results: Expression analysis revealed that CaMKII delta, both cytosolic delta(C) and nuclear delta(B) splice variants, were significantly increased in both right and left ventricles from patients with dilated or ischemic cardiomyopathy versus nonfailing. Experiments with isometrically twitching trabeculae revealed significantly improved force frequency relationships in the presence of CaMKII inhibitors (KN-93 and AIP). Increased postrest twitches after CaMKII inhibition indicated an improved sarcoplasmic reticulum (SR) Ca2+ loading. This was confirmed in isolated myocytes by a reduced SR Ca2+ spark frequency and hence SR Ca2+ leak, resulting in increased SR Ca2+ load when inhibiting CaMKII. Ryanodine receptor type 2 phosphorylation at Ser2815, which is known to be phosphorylated by CaMKII thereby contributing to SR Ca2+ leak, was found to be markedly reduced in KN-93-treated trabeculae. Interestingly, CaMKII inhibition did not influence contractility in nonfailing sheep trabeculae. Conclusions: The present study shows for the first time that CaMKII inhibition acutely improves contractility in human HF where CaMKII delta expression is increased. The mechanism proposed consists of a reduced SR Ca2+ leak and consequently increased SR Ca2+ load. Thus, CaMKII inhibition appears to be a possible therapeutic option for patients with HF and merits further investigation. (Circ Res. 2010;107:1150-1161.)"],["dc.identifier.doi","10.1161/CIRCRESAHA.110.220418"],["dc.identifier.gro","3142840"],["dc.identifier.isi","000283583400015"],["dc.identifier.pmid","20814023"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6154"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/288"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0009-7330"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Inhibition of Elevated Ca2+/Calmodulin-Dependent Protein Kinase II Improves Contractility in Human Failing Myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","359"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Clinical Research in Cardiology"],["dc.bibliographiccitation.lastpage","368"],["dc.bibliographiccitation.volume","99"],["dc.contributor.author","Sohns, Christian"],["dc.contributor.author","Sossalla, Samuel T."],["dc.contributor.author","Schmitto, Jan Dieter"],["dc.contributor.author","Jacobshagen, Claudius"],["dc.contributor.author","Raab, Bjoern-Werner"],["dc.contributor.author","Obenauer, Silvia"],["dc.contributor.author","Maier, Lars. S."],["dc.date.accessioned","2018-11-07T08:42:29Z"],["dc.date.available","2018-11-07T08:42:29Z"],["dc.date.issued","2010"],["dc.description.abstract","Hypertrophic obstructive cardiomyopathy (HOCM) is treated by surgical myectomy or transcoronary ablation of septal hypertrophy (TASH). The aim of this study was to visualize the feasibility, success and short-term results of TASH on the basis of cardiac MRI (CMR) in comparison with cardiac catheterization and echocardiography. In this in vivo study, nine patients with HOCM were treated with TASH. Patients were evaluated by transthoracic echocardiography, invasive cardiac angiography and CMR. Follow-up examinations were carried out after 1, 3 and 12 months. MR imaging was performed on a 1.5-T scanner. All images were processed using the semiautomatic Argus software and were evaluated by an attending thoracic radiologist and cardiologist. The echocardiographic pressure gradient (at rest) was 69.3 +/- A 15.3 mmHg before and 22.1 +/- A 5.7 mmHg after TASH (P < 0.01, n = 9). The flux acceleration over the aortic valve examined (V (max)) was 5.1 +/- A 0.6 m/s before and 3.4 +/- A 0.3 m/s after the TASH procedure (P < 0.05). Also, there was a decrease of septum thickness from 22.0 +/- A 1.2 to 20.2 +/- A 1.0 mm (P < 0.05) after 6 +/- A 3 weeks. The invasively assessed pressure gradient at rest was reduced from 63.7 +/- A 15.2 to 21.2 +/- A 11.1 mmHg (P < 0.01) and the post-extrasystolic gradient was reduced from 138.9 +/- A 12.7 to 45.6 +/- A 16.5 mmHg (P < 0.01). All differences as well as the quantity of injected ethanol were plotted against the size or amount of scar tissue as assessed in the MRI. There was a statistically significant correlation between the post-extrasystolic gradient decrease and the amount of scar tissue (P = 0.03, r (2) = 0.5). In addition, the correlation between the quantity of ethanol and scar tissue area was highly significant (P < 0.01, r (2) = 0.6), whereas the values for the gradient deviation (P = 0.10, r (2) = 0.34), Delta V (max) (P = 0.12, r (2) = 0.31), as well as the gradient at rest (P = 0.27, r (2) = 0.17) were not significant. TASH was consistently effective in reducing the gradient in all patients with HOCM. In contrast to the variables investigated by echocardiography, the invasively measured post-extrasystolic gradient correlated much better with the amount of scar tissue as assessed by CMR. We conclude that the optimal modality to visualize the TASH effect seems to be a combination of CMR and the invasive identification of the post-extrasystolic gradient."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft (DFG) [MA 1982/2-2, MA 1982/4-1]"],["dc.identifier.doi","10.1007/s00392-010-0128-8"],["dc.identifier.isi","000278089000002"],["dc.identifier.pmid","20503122"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/4241"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19712"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","1861-0684"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Visualization of transcoronary ablation of septal hypertrophy in patients with hypertrophic obstructive cardiomyopathy: a comparison between cardiac MRI, invasive measurements and echocardiography"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]