Maier, Lars Siegfried

[["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.issue","1"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","80"],["dc.contributor.author","Maier, Lars. S."],["dc.contributor.author","Franz, W. M."],["dc.contributor.author","Horn, W. C."],["dc.contributor.author","Weichert, S."],["dc.contributor.author","Pieske, Burkert M."],["dc.date.accessioned","2018-11-07T09:30:12Z"],["dc.date.available","2018-11-07T09:30:12Z"],["dc.date.issued","2001"],["dc.format.extent","599A"],["dc.identifier.isi","000166692202728"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31248"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biophysical Society"],["dc.publisher.place","Bethesda"],["dc.relation.issn","0006-3495"],["dc.title","SERCA28-overexpression improves force-frequency and post-rest behavior due to increased SR Ca-content in transgenic rats"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S63"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","S64"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Mehel, Hind"],["dc.contributor.author","Emons, J."],["dc.contributor.author","Vettel, Christiane"],["dc.contributor.author","Lechene, Patrick"],["dc.contributor.author","Maier, Lars. S."],["dc.contributor.author","Nikolaev, V. O."],["dc.contributor.author","Vandecasteele, Gregoire"],["dc.contributor.author","Fischmeister, Rodolphe"],["dc.contributor.author","Elarmouche, A."],["dc.date.accessioned","2018-11-07T09:25:42Z"],["dc.date.available","2018-11-07T09:25:42Z"],["dc.date.issued","2013"],["dc.identifier.isi","000332489100237"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30127"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.title","Phoshodiesterase-2 is Upregulated in Human Failing Hearts and Blunts Beta-Adrenergic Responses in Cardiomyocytes"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2586"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Molecular and Cellular Biology"],["dc.bibliographiccitation.lastpage","2602"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Scharf, Madeleine"],["dc.contributor.author","Neef, Stefan"],["dc.contributor.author","Freund, Robert"],["dc.contributor.author","Geers-Knoerr, Cornelia"],["dc.contributor.author","Franz-Wachtel, Mirita"],["dc.contributor.author","Brandis, Almuth"],["dc.contributor.author","Krone, Dorothee"],["dc.contributor.author","Schneider, Heike"],["dc.contributor.author","Groos, Stephanie"],["dc.contributor.author","Menon, Manoj B."],["dc.contributor.author","Chang, Kin-Chow"],["dc.contributor.author","Kraft, Theresia"],["dc.contributor.author","Meissner, Joachim D."],["dc.contributor.author","Boheler, Kenneth R."],["dc.contributor.author","Maier, Lars. S."],["dc.contributor.author","Gaestel, Matthias"],["dc.contributor.author","Scheibe, Renate J."],["dc.date.accessioned","2018-11-07T09:23:26Z"],["dc.date.available","2018-11-07T09:23:26Z"],["dc.date.issued","2013"],["dc.description.abstract","The mitogen-activated protein kinase (MAPK)-activated protein kinases 2 and 3 (MK2/3) represent protein kinases downstream of the p38 MAPK. Using MK2/3 double-knockout (MK2/3(-/-)) mice, we analyzed the role of MK2/3 in cross-striated muscle by transcriptome and proteome analyses and by histology. We demonstrated enhanced expression of the slow oxidative skeletal muscle myofiber gene program, including the peroxisome proliferator-activated receptor gamma (PPAR gamma) coactivator 1 alpha (PGC-1 alpha). Using reporter gene and electrophoretic gel mobility shift assays, we demonstrated that MK2 catalytic activity directly regulated the promoters of the fast fiber-specific myosin heavy-chain IId/x and the slow fiber-specific sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2) gene. Elevated SERCA2a gene expression caused by a decreased ratio of transcription factor Egr-1 to Sp1 was associated with accelerated relaxation and enhanced contractility in MK2/3(-/-) cardiomyocytes, concomitant with improved force parameters in MK2/3(-/-) soleus muscle. These results link MK2/3 to the regulation of calcium dynamics and identify enzymatic activity of MK2/3 as a critical factor for modulating cross-striated muscle function by generating a unique muscle phenotype exhibiting both reduced fatigability and enhanced force in MK2/3(-/-) mice. Hence, the p38-MK2/3 axis may represent a novel target for the design of therapeutic strategies for diseases related to fiber type changes or impaired SERCA2 function."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [SCHE 309/5-1]"],["dc.identifier.doi","10.1128/MCB.01692-12"],["dc.identifier.isi","000320030900007"],["dc.identifier.pmid","23608535"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29577"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Microbiology"],["dc.relation.issn","0270-7306"],["dc.title","Mitogen-Activated Protein Kinase-Activated Protein Kinases 2 and 3 Regulate SERCA2a Expression and Fiber Type Composition To Modulate Skeletal Muscle and Cardiomyocyte"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1134"],["dc.bibliographiccitation.issue","15"],["dc.bibliographiccitation.journal","European Heart Journal"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Kensah, George"],["dc.contributor.author","Lara, Angelica Roa"],["dc.contributor.author","Dahlmann, Julia"],["dc.contributor.author","Zweigerdt, Robert"],["dc.contributor.author","Schwanke, Kristin"],["dc.contributor.author","Hegermann, Jan"],["dc.contributor.author","Skvorc, David"],["dc.contributor.author","Gawol, Anke"],["dc.contributor.author","Azizian, Azadeh"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Maier, Lars. S."],["dc.contributor.author","Krause, Andreas"],["dc.contributor.author","Draeger, Gerald"],["dc.contributor.author","Ochs, Matthias"],["dc.contributor.author","Haverich, Axel"],["dc.contributor.author","Gruh, Ina"],["dc.contributor.author","Martin, Ulrich"],["dc.date.accessioned","2018-11-07T09:26:20Z"],["dc.date.available","2018-11-07T09:26:20Z"],["dc.date.issued","2013"],["dc.description.abstract","We explored the use of highly purified murine and human pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) to generate functional bioartificial cardiac tissue (BCT) and investigated the role of fibroblasts, ascorbic acid (AA), and mechanical stimuli on tissue formation, maturation, and functionality. Murine and human embryonic/induced PSC-derived CMs were genetically enriched to generate three-dimensional CM aggregates, termed cardiac bodies (CBs). Addressing the critical limitation of major CM loss after single-cell dissociation, non-dissociated CBs were used for BCT generation, which resulted in a structurally and functionally homogenous syncytium. Continuous in situ characterization of BCTs, for 21 days, revealed that three critical factors cooperatively improve BCT formation and function: both (i) addition of fibroblasts and (ii) ascorbic acid supplementation support extracellular matrix remodelling and CB fusion, and (iii) increasing static stretch supports sarcomere alignment and CM coupling. All factors together considerably enhanced the contractility of murine and human BCTs, leading to a so far unparalleled active tension of 4.4 mN/mm(2) in human BCTs using optimized conditions. Finally, advanced protocols were implemented for the generation of human PSC-derived cardiac tissue using a defined animal-free matrix composition. BCT with contractile forces comparable with native myocardium can be generated from enriched, PSC-derived CMs, based on a novel concept of tissue formation from non-dissociated cardiac cell aggregates. In combination with the successful generation of tissue using a defined animal-free matrix, this represents a major step towards clinical applicability of stem cell-based heart tissue for myocardial repair."],["dc.identifier.doi","10.1093/eurheartj/ehs349"],["dc.identifier.isi","000318077500012"],["dc.identifier.pmid","23103664"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30278"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0195-668X"],["dc.title","Murine and human pluripotent stem cell-derived cardiac bodies form contractile myocardial tissue in vitro"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","385"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","108"],["dc.contributor.author","Sag, Can Martin"],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Neumann, Kay"],["dc.contributor.author","Opiela, Marie-Kristin"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Steuer, Felicia"],["dc.contributor.author","Sowa, Thomas"],["dc.contributor.author","Gupta, Shamindra"],["dc.contributor.author","Schirmer, Markus"],["dc.contributor.author","Huenlich, Mark"],["dc.contributor.author","Rave-Fraenk, Margret"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Anderson, Mark E."],["dc.contributor.author","Shah, Ajay M."],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2018-11-07T09:19:46Z"],["dc.date.available","2018-11-07T09:19:46Z"],["dc.date.issued","2013"],["dc.description.abstract","Ionizing radiation (IR) is an integral part of modern multimodal anti-cancer therapies. IR involves the formation of reactive oxygen species (ROS) in targeted tissues. This is associated with subsequent cardiac dysfunction when applied during chest radiotherapy. We hypothesized that IR (i.e., ROS)-dependently impaired cardiac myocytes' Ca handling might contribute to IR-dependent cardiocellular dysfunction. Isolated ventricular mouse myocytes and the mediastinal area of anaesthetized mice (that included the heart) were exposed to graded doses of irradiation (sham 4 and 20 Gy) and investigated acutely (after similar to 1 h) as well as chronically (after similar to 1 week). IR induced a dose-dependent effect on myocytes' systolic function with acutely increased, but chronically decreased Ca transient amplitudes, which was associated with an acutely unaltered but chronically decreased sarcoplasmic reticulum (SR) Ca load. Likewise, in vivo echocardiography of anaesthetized mice revealed acutely enhanced left ventricular contractility (strain analysis) that declined after 1 week. Irradiated myocytes showed persistently increased diastolic SR Ca leakage, which was acutely compensated by an increase in SR Ca reuptake. This was reversed in the chronic setting in the face of slowed relaxation kinetics. As underlying cause, acutely increased ROS levels were identified to activate Ca/calmodulin-dependent protein kinase II (CaMKII). Accordingly, CaMKII-, but not PKA-dependent phosphorylation sites of the SR Ca release channels (RyR2, at Ser-2814) and phospholamban (at Thr-17) were found to be hyperphosphorylated following IR. Conversely, ROS-scavenging as well as CaMKII-inhibition significantly attenuated CaMKII-activation, disturbed Ca handling, and subsequent cellular dysfunction upon irradiation. Targeted cardiac irradiation induces a biphasic effect on cardiac myocytes Ca handling that is associated with chronic cardiocellular dysfunction. This appears to be mediated by increased oxidative stress and persistently activated CaMKII. Our findings suggest impaired cardiac myocytes Ca handling as a so far unknown mediator of IR-dependent cardiac damage that might be of relevance for radiation-induced cardiac dysfunction."],["dc.identifier.doi","10.1007/s00395-013-0385-6"],["dc.identifier.isi","000324877000001"],["dc.identifier.pmid","24068185"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10300"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28721"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/51"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["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","0300-8428"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Ionizing radiation regulates cardiac Ca handling via increased ROS and activated CaMKII"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","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","267"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Clinical Research in Cardiology"],["dc.bibliographiccitation.lastpage","276"],["dc.bibliographiccitation.volume","99"],["dc.contributor.author","Jacobshagen, Claudius"],["dc.contributor.author","Pelster, Theresa"],["dc.contributor.author","Pax, Anja"],["dc.contributor.author","Horn, Wiebke"],["dc.contributor.author","Schmidt-Schweda, Stephan"],["dc.contributor.author","Unsoeld, Bernhard W."],["dc.contributor.author","Seidler, Tim"],["dc.contributor.author","Wagner, Stephan"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.date.accessioned","2017-09-07T11:46:04Z"],["dc.date.available","2017-09-07T11:46:04Z"],["dc.date.issued","2010"],["dc.description.abstract","Post-cardiac arrest myocardial dysfunction is a common phenomenon after return of spontaneous circulation (ROSC) and contributes to hemodynamic instability and low survival rates after cardiac arrest. Mild hypothermia for 24 h after ROSC has been shown to significantly improve neurologic recovery and survival rates. In the present study we investigate the influence of therapeutic hypothermia on hemodynamic parameters in resuscitated patients and on contractility in failing human myocardium. We analyzed hemodynamic data from 200 cardiac arrest survivors during the hypothermia period. The initial LVEF was 32.6 +/- A 1.2% indicating a significantly impaired LV function. During hypothermia induction, the infusion rate of epinephrine could be significantly reduced from 9.1 +/- A 1.3 mu g/min [arrival intensive care unit (ICU) 35.4A degrees C] to 4.6 +/- A 1.0 mu g/min (34A degrees C) and 2.8 +/- A 0.5 mu g/min (33A degrees C). The dobutamine and norepinephrine application rates were not changed significantly. The mean arterial blood pressure remained stable. The mean heart rate significantly decreased from 91.8 +/- A 1.7 bpm (arrival ICU) to 77.3 +/- A 1.5 bpm (34A degrees C) and 70.3 +/- A 1.4 bpm (33A degrees C). In vitro we investigated the effect of hypothermia on isolated ventricular muscle strips from explanted failing human hearts. With decreasing temperature, the contractility increased to a maximum of 168 +/- A 23% at 27A degrees C (n = 16, P < 0.05). Positive inotropic response to hypothermia was accompanied by moderately increased rapid cooling contractures as a measure of sarcoplasmic reticulum (SR) Ca(2+) content, but can be elicited even when the SR Ca(2+) release is blocked in the presence of ryanodine. Contraction and relaxation kinetics are prolonged with hypothermia, indicating increased Ca(2+) sensitivity as the main mechanism responsible for inotropy. In conclusion, mild hypothermia stabilizes hemodynamics in cardiac arrest survivors which might contribute to improved survival rates in these patients. Mechanistically, we demonstrate that hypothermia improves contractility in failing human myocardium most likely by increasing Ca(2+)-sensitivity."],["dc.identifier.doi","10.1007/s00392-010-0113-2"],["dc.identifier.gro","3142931"],["dc.identifier.isi","000277014600001"],["dc.identifier.pmid","20130890"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/4240"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/389"],["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","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","1861-0684"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human 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"]]