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  • Oxford University Press (OUP)  (3)
  • 1
    Online Resource
    Online Resource
    Effective termination of atrial fibrillation by SK channel inhibition is associated with a sudden organization of fibrillatory conduction
    Oxford University Press (OUP) ; 2021
    In:  EP Europace Vol. 23, No. 11 ( 2021-11-08), p. 1847-1859
    Details
    In: EP Europace, Oxford University Press (OUP), Vol. 23, No. 11 ( 2021-11-08), p. 1847-1859
    Abstract: Pharmacological termination of atrial fibrillation (AF) remains a challenge due to limited efficacy and potential ventricular proarrhythmic effects of antiarrhythmic drugs. SK channels are proposed as atrial-specific targets in the treatment of AF. Here, we investigated the effects of the new SK channel inhibitor AP14145. Methods and results Eight goats were implanted with pericardial electrodes for induction of AF (30 days). In an open-chest study, the atrial conduction velocity (CV) and effective refractory period (ERP) were measured during pacing. High-density mapping of both atrial free-walls was performed during AF and conduction properties were assessed. All measurements were performed at baseline and during AP14145 infusion [10 mg/kg/h (n = 1) or 20 mg/kg/h (n = 6)]. At an infusion rate of 20 mg/kg/h, AF terminated in five of six goats. AP14145 profoundly increased ERP and reduced CV during pacing. AP14145 increased spatiotemporal instability of conduction at short pacing cycle lengths. Atrial fibrillation cycle length and pathlength (AF cycle length × CV) underwent a strong dose-dependent prolongation. Conduction velocity during AF remained unchanged and conduction patterns remained complex until the last seconds before AF termination, during which a sudden and profound organization of fibrillatory conduction occurred. Conclusion AP14145 provided a successful therapy for termination of persistent AF in goats. During AF, AP14145 caused an ERP and AF cycle length prolongation. AP14145 slowed CV during fast pacing but did not lead to a further decrease during AF. Termination of AF was preceded by an abrupt organization of AF with a decline in the number of fibrillation waves.
    Type of Medium: Online Resource
    ISSN: 1099-5129 , 1532-2092
    URL: Article
    DOI: 10.1093/europace/euab125
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2002579-8
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  • 2
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    The productivity effects of labor market deregulation: evidence from German firms during 2010–2019
    Oxford University Press (OUP) ; 2024
    In:  Industrial and Corporate Change ( 2024-05-23)
    Details
    In: Industrial and Corporate Change, Oxford University Press (OUP), ( 2024-05-23)
    Abstract: In the early 2000s, the German government introduced the Hartz reforms, which deregulated German labor markets. These reforms were praised internationally as striking a balance between job growth and productivity growth. While macroeconomic research has shown that the reforms have indeed lowered German unemployment, their effects on labor productivity need to be better understood. This paper addresses the impact of temporary agency work (TAW) on German labor productivity during 2010–2019, based on data from a firm-level panel of the German Institute for Employment Research (IAB). It contributes to the rising number of firm-level studies by extending their results in a broader temporal perspective, during which TAW intensities have increased substantially, especially in TAW-using firms. The system generalized method of moment (GMM) estimations based on a firm-level data set with 13,197 observations for the period 2010–2019 show that a robust hump-shaped relationship exists between the extent of TAW and the firms’ labor productivity. We find that the increase in the use of TAWs following the Hartz reforms has, on average, positively contributed to labor productivity growth in German firms. However, the findings also show that if numerical flexibility is increased too much, productivity growth in Germany will suffer. This is particularly the case for several industrial sectors that are important in the German economy. These results are important given recent calls for more labor market flexibility to help firms grow in an increasingly turbulent global economy.
    Type of Medium: Online Resource
    ISSN: 0960-6491 , 1464-3650
    URL: Article
    DOI: 10.1093/icc/dtae024
    RVK:
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 1494333-5
    SSG: 3,2
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  • 3
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    Synergistic antiarrhythmic effect of inward rectifier current inhibition and pulmonary vein isolation in a 3D computer model for atrial fibrillation
    Oxford University Press (OUP) ; 2021
    In:  EP Europace Vol. 23, No. Supplement_1 ( 2021-03-04), p. i161-i168
    Details
    In: EP Europace, Oxford University Press (OUP), Vol. 23, No. Supplement_1 ( 2021-03-04), p. i161-i168
    Abstract: Recent clinical studies showed that antiarrhythmic drug (AAD) treatment and pulmonary vein isolation (PVI) synergistically reduce atrial fibrillation (AF) recurrences after initially successful ablation. Among newly developed atrial-selective AADs, inhibitors of the G-protein-gated acetylcholine-activated inward rectifier current (IKACh) were shown to effectively suppress AF in an experimental model but have not yet been evaluated clinically. We tested in silico whether inhibition of inward rectifier current or its combination with PVI reduces AF inducibility. Methods and results We simulated the effect of inward rectifier current blockade (IK blockade), PVI, and their combination on AF inducibility in a detailed three-dimensional model of the human atria with different degrees of fibrosis. IK blockade was simulated with a 30% reduction of its conductivity. Atrial fibrillation was initiated using incremental pacing applied at 20 different locations, in both atria. IK blockade effectively prevented AF induction in simulations without fibrosis as did PVI in simulations without fibrosis and with moderate fibrosis. Both interventions lost their efficacy in severe fibrosis. The combination of IK blockade and PVI prevented AF in simulations without fibrosis, with moderate fibrosis, and even with severe fibrosis. The combined therapy strongly decreased the number of fibrillation waves, due to a synergistic reduction of wavefront generation rate while the wavefront lifespan remained unchanged. Conclusion Newly developed blockers of atrial-specific inward rectifier currents, such as IKAch, might prevent AF occurrences and when combined with PVI effectively supress AF recurrences in human.
    Type of Medium: Online Resource
    ISSN: 1099-5129 , 1532-2092
    URL: Article
    DOI: 10.1093/europace/euaa413
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2002579-8
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