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Available from: Cevher Ozcan, Jan 09, 2014
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    • "AF remain unclear. While recent studies have identified a familial form of AF [8], the majority of patients with AF have the common form with no defined genetic susceptibility. Here, we summarize recent findings in AF pathogenesis, particularly those related to the structural and electrical remodeling that occurs throughout the disease process. "
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    ABSTRACT: Atrial fibrillation (AF) is the most common arrhythmia and is associated with a high risk of morbidity and mortality. However, there are limited treatment strategies for prevention of disease onset and progression. Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process. Translational and clinical studies conducted over the past twenty years have revealed that atrial remodeling in AF shares several important pathophysiologic traits with the remodeling processes exhibited by hibernating myocardium that develop in response to chronic ischemia. These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival. In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm. Ultimately, better understanding of the molecular mechanisms of atrial myocyte remodeling during the onset of AF and the transition from paroxysmal to persistent stages of the disease may facilitate discovery of new therapeutic targets.
    07/2015; 2015(21):587361. DOI:10.1155/2015/587361
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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 · 5.04 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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