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Our findings suggest that RDN is feasible even in cardiac unstable patients. Randomized controlled trials are urgently needed to study the effects of RD in patients with electrical storm and CHF.

The plasmid-encoded surface protein YadA of Yersinia enterocolitica mediates binding to diverse extracellular matrix (ECM) proteins, adherence to epithelial cell lines, resistance to complement lysis, autoagglutination, and is required for mouse virulence. Using site-directed mutagenesis we attempted to analyse the relationship between structural domains and functions of YadA. In a first approach we could abrogate collagen binding by chemical modification of histidyl residues of YadA protein. This result prompted us to substitute histidyl residues (His) of conserved regions of YadA protein of Y. enterocolitica O8 by tyrosine residues using site-directed mutagenesis. Substitution of His-156 and His-159 (YadA-2 mutant) resulted in abrogation of binding to ECM proteins, of cell adherence, and in reduction of mouse virulence, whereas autoagglutination, serum complement resistance and oligomer formation remained unaffected. A striking result was obtained from the orogastric mouse-infection model: the YadA-2 mutant retained the ability to colonize the small intestine and to invade and multiply within the Peyer's patches but was impaired in colonizing mesenteric lymph nodes and spleen in comparison to the wild-type strain.

Abstract-The aim of this study was to identify the relative impact of adrenergic and cholinergic activity on atrial fibrillation (AF) inducibility and blood pressure (BP) in a model for obstructive sleep apnea. Obstructive sleep apnea is associated with sympathovagal disbalance, AF, and postapneic BP rises. Renal denervation (RDN) reduces renal efferent and possibly also afferent sympathetic activity and BP in resistant hypertension. The effects of RDN compared with ␤-blockade by atenolol on atrial electrophysiological changes, AF inducibility, and BP during obstructive events and on shortening of atrial effective refractory period 5 Severe bradycardia and atrioventricular conduction disturbances together with postapneic blood pressure (BP) rises during the arousal are frequently seen in OSA and suggest sympathovagal activation. 6,7 Although enhanced vagal tone is known to induce shortening of the atrial effective refractory period (AERP), increased sympathetic tone may increase spontaneous triggered activity, both of which, when simultaneously occurring, could induce and maintain AF. 8 In addition, repetitive postapneic BP surges may lead to atrial structural changes and, thus, an arrhythmogenic substrate for AF. Previously, we showed that negative tracheal pressure (NTP) during obstructive respiratory events leads to pronounced shortening of the AERP, thereby perpetuating AF.9 These electrophysiological changes were mainly mediated by increased vagal tone because they were completely inhibited by atropine or bilateral vagotomy. However, less is known about the relative impact of adrenergic and cholinergic activity on AF inducibility and maintenance in OSA. We hypothesized that modulation of the sympathetic nervous system might reduce AF susceptibility and postapneic BP rises in OSA. Renal denervation is a new therapeutic approach to reduce sympathetic activity, BP, and apnea-hypopnea index (OSA severity) in resistant hypertension. [10][11][12][13] However, the effect of RDN on AF inducibility and BP during and after obstructive events is unknown. We tested the effect of denervation of the afferent and efferent renal sympathetic nerves shown previously to reduce renal and whole body sympathetic activity 10-12 and compared it with ␤-receptor blockade by atenolol on atrial electrophysiological changes and postapneic BP rises in a pig model for OSA. To check whether RDN displays its

Background-The mechanisms of the atrial contractile dysfunction induced by atrial fibrillation (AF) are not completely understood. In particular, the relation between the atrial dysfunction and electrical remodeling has not yet been studied. Methods and Results-Seven goats were chronically instrumented with electrodes sutured to the atria and with ultrasonic piezoelectric crystals to record the atrial diameters. A pressure transducer was implanted in the right atrium. After 5 minutes, 3 hours, and throughout the first 5 days of artificially maintained AF, atrial contractile function was measured and the atrial effective refractory period (AERP) was monitored for comparison. Also, the positive inotropic effects of the L-type Ca 2ϩ -channel agonist BayY5959 and short trains of rapid atrial pacing were studied. After resumption of sinus rhythm, the recovery of atrial contractile function was followed. After 5 minutes of AF, atrial contractility was decreased by Ϸ55% but recovered completely within 10 minutes. Five days of AF nearly completely abolished the atrial contractile function, and recovery took 2 days. During the first days of AF, the development of the contractile dysfunction followed the same time course as the shortening of AERP (electrical remodeling). In remodeled atria, BayY5959 increased atrial contractility to the same extent as it prolonged AERP. The inotropic effect of short trains of rapid atrial pacing was similar in normal and remodeled atria. Conclusions-Depending on the duration of AF, different mechanisms contribute to the AF-induced atrial hypocontractility. Atrial contractile remodeling during several days of AF goes hand in hand with electrical remodeling and might be caused by a reduction of the L-type Ca

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Aldosterone causes a substrate for atrial arrhythmias characterized by atrial fibrosis, myocyte hypertrophy, and conduction disturbances. The described model imputes atrial proarrhythmia directly to aldosterone, since ventricular haemodynamics appeared unaltered in this model. This mechanism may have therapeutical impact for primary and secondary prevention of AF.