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Available from: Cevher Ozcan, Jan 09, 2014
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    • "Last but not least, genetic factors appear to play a role in 'lone' atrial fibrillation, i.e. AF in the absence of any heart disease (for reviews see Lubitz et al. 2010 and Magnani et al. 2011). Mutations in ion channels that associate with familial AF are reported to induce both loss and gain of function. "
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    ABSTRACT: New antiarrhythmic drugs for treatment of atrial fibrillation should ideally be atrial selective in order to avoid pro-arrhythmic effects in the ventricles. Currently recognized atrial selective targets include atrial Nav1.5 channels, Kv1.5 channels and constitutively active Kir3.1/3.4 channels each of which confers atrial selectivity by different mechanisms. Na+ channel blockers with potential- and frequency-dependent action preferentially suppress atrial fibrillation because of the high excitation rate and less negative atrial resting potential, which promote drug binding in atria. Kv1.5 channels are truly atrial-selective because they do not conduct repolarising current IKur in ventricles. Constitutively active IK,ACh is predominantly observed in remodelled atria from patients in permanent AF. A lot of effort has been invested to detect compounds which will selectively block Kir3.1/Kir3.4 in their remodelled constitutively active form. Novel drugs which have been and are being developed that aim at atrial-selective targets. Vernakalant and ranolazine which mainly block atrial Na+ channels are clinically effective. Newly designed selective IKur blockers and IK,ACh blockers are effective in animal models, however, clinical benefit in converting AF into SR or reducing AF burden remains to be demonstrated. In conclusion, atrial-selective antiarrhythmic agents have a lot of potential, but a long way to go.
    The Journal of Physiology 06/2013; 591(17). DOI:10.1113/jphysiol.2013.256115 · 4.54 Impact Factor
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    ABSTRACT: We propose a novel type of closing semiconductor switches based on a new physical mechanism-the propagation of a superfast tunneling-assisted impact ionization front. We present numerical simulations of the switching transients in the proposed devices. Our numerical results suggest that with the new mechanism, voltage pulses with a ramp up to 500 kV/ns and amplitude up to 8 kV can be formed. This sets new frontiers in pulse power electronics.
    Power Modulator Symposium, 2002 and 2002 High-Voltage Workshop. Conference Record of the Twenty-Fifth International; 01/2007
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    ABSTRACT: Atrial fibrillation (AF) is the most common sustained arrhythmia and has a substantial heritable component. Numerous associations between single nucleotide polymorphisms (SNPs) and AF have been described, but few have been replicated. We sought to systematically replicate SNPs that are reported to be associated with AF in two large study samples of European descent. We searched PubMed for studies reporting associations between SNPs and AF published before July 1, 2007. SNPs were genotyped in two independent case-control samples from Germany and the United States. Associations between SNPs and AF were assessed using logistic regression models adjusting for age, sex, and hypertension. A meta-analysis of the results from the two studies was performed. We identified 21 SNPs and the angiotensin-converting enzyme insertion/deletion polymorphism that were reported to be associated with AF in the literature. Nine of these genetic variants were not represented on common genome-wide SNP arrays. We successfully genotyped 21 of these 22 variants in 2,145 cases with AF from the German Competence Network for Atrial Fibrillation and 4,073 controls from the KORA S4 study and 16 variants in 790 cases and 1,330 controls from the Massachusetts General Hospital. None of the SNPs replicated in independent populations with AF. Our results suggest that previously reported associations to AF were likely false positives and highlight the need for systematic replication of genetic associations in large, independent cohorts to accurately detect variants associated with disease.
    Heart rhythm: the official journal of the Heart Rhythm Society 11/2010; 8(3):403-9. DOI:10.1016/j.hrthm.2010.11.003 · 4.92 Impact Factor
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