Canine model of paroxysmal atrial fibrillation and paroxysmal atrial tachycardia

Both autonomic nerve activity and electrical remodeling are important in atrial arrhythmogenesis. Therefore, dogs with sympathetic hyperinnervation, myocardial infarction (MI), and complete atrioventricular block (CAVB) may have a high incidence of atrial arrhythmias. We studied eight dogs (experimental group) with MI, CAVB, and sympathetic hyperinnervation induced either by nerve growth factor infusion (n = 4 dogs) or subthreshold electrical stimulation (n = 4 dogs) of the left stellate ganglion. Cardiac rhythm was continuously monitored by a Data Sciences International transmitter for 48 (SD 27) days. Three normal control dogs were also monitored. Six additional normal dogs were used for histology control. Paroxysmal atrial fibrillation (PAF) and paroxysmal atrial tachycardia (PAT) were documented in all dogs in the experimental group, with an average of 3.8 (SD 3) episodes/day, including 1.3 (SD 1.6) episodes of PAF and 2.5 (SD 2.2) episodes of PAT. The duration averaged 298 (SD 745) s (range, 7-4,000 s). There was a circadian pattern of arrhythmia onset (P < 0.01). Of 576 episodes of PAF and PAT, 236 (41%) episodes occurred during either sustained or nonsustained ventricular tachycardia (VT). Among these 236 episodes, 53% started before VT, whereas 47% started after the onset of VT. Normal dogs did not have either PAF or PAT. The hearts from the experimental group had a higher density of nerve structures immunopositive (P < 0.01) for three different nerve specific markers in both right and left atria than those of the control dogs. We conclude that the induction of nerve sprouting and sympathetic hyperinnervation in dogs with CAVB and MI creates a high yield model of PAF and PAT.     

ABC of atrial fibrillation. Antithrombotic treatment for atrial fibrillation.

Antithrombotic prophylaxis with long term warfarin or aspirin reduces thromboembolic risk in atrial fibrillation. Identification, risk assessment, and regular review of all patients with atrial fibrillation should be routine in general and hospital practice. Risk stratification is easily performed on clinical grounds--echocardiography may refine it.     

Cdk7: Open questions beyond the prevailing model

Comment on: Ganuza M, et al. EMBO J 2012; 31:2498-510.     

Atrial remodeling in atrial fibrillation and association between microRNA network and atrial fibrillation

Atrial fibrillation (AF) remains one of the leading causes of morbidity and mortality in the world which are related to palpitations, fainting, congestive heart failure or stroke. The mechanism for atrial fibrillation has been identified as electrical remodeling, structure remodeling and intracellular calcium handling remodeling. microRNAs (miRNAs) have recently emerged as one of the important factors in regulating gene expression. So far, thousands of miRNA genes have been found in diverse animals with the function of regulating cell death, cell proliferation, haematopoiesis and even participate in the processing of cardiovascular disease. In this review, we summarize the mechanism of AF and the association of microRNAs network with AF. We provide a potential perspective of miRNAs as the therapeutic target for AF.     

Cryoballoon ablation for atrial fibrillation

Focal point-by-point radiofrequency catheter ablation has shown considerable success in the treatment of paroxysmal atrial fibrillation. However, it is not without limitations. Recent clinical and preclinical studies have demonstrated that cryothermal ablation using a balloon catheter (Artic Front©, Medtronic CryoCath LP) provides an effective alternative strategy to treating atrial fibrillation. The objective of this article is to review efficacy and safety data surrounding cryoballoon ablation for paroxysmal and persistent atrial fibrillation. In addition, a practical step-by-step approach to cryoballoon ablation is presented, while highlighting relevant literature regarding: 1) the rationale for adjunctive imaging, 2) selection of an appropriate cryoballoon size, 3) predictors of efficacy, 4) advanced trouble-shooting techniques, and 5) strategies to reduce procedural complications, such as phrenic nerve palsy.     

Chick embryonic cells as a source for generating in vitro model of muscle cell dystrophy

Chick embryonic cells can be used to develop an easy and economical in vitro model for conducting studies on the disease muscle dystrophy (MD). For this, the limb myoblasts from 11th day chick embryo were isolated and cultured. To this muscle cell culture, anti-dystroglycan antibody (IIH6) was added so as to target the α-dystroglycan and disrupt the connection between the cytoskeletal proteins and the extracellular matrix (which is a characteristic feature of MD). Cells were allowed to differentiate further and the morphometrics and mRNA expression were studied. The IIH6-treated muscle cells displayed changes in morphometry, contractibility, and also atrophy was observed when compared to the control cultures. Concomitant gene expression studies showed an upregulation in TGF-β expression, while the muscle sculpture genes MYOD1, MYF5, LAMA2 and MYOG were downregulated resembling the MD in vivo. This simple and cost-effective method can be useful in studies to further understand the disease mechanism and also in conducting initial studies on effect of novel pharmacological agents.     

Direction-dependent conduction abnormalities in a canine model of atrial fibrillation due to chronic atrial dilatation

Chronic rapid atrial pacing (RAP) leads to changes that perpetuate atrial fibrillation (AF). Chronic atrial dilatation due to mitral regurgitation (MR) also increases AF inducibility, but it is not clear whether the underlying mechanism is similar. Therefore, we have investigated atrial electrophysiology in a canine MR model (mitral valve avulsion, 1 mo) using high-resolution optical mapping and compared it with control dogs and with the canine RAP model (6-8 wk of atrial pacing at 600 beats/min, atrioventricular block, and ventricular pacing at 100 beats/min). At followup, optical action potentials were recorded using a 16 x 16 photodiode array from 2 x 2-cm left atrial (LA) and right atrial (RA) areas in perfused preparations, with pacing electrodes around the field of view to study direction dependency of conduction. Action potential duration at 80% repolarization (APD(80)) was not different between control and MR but was reduced in RAP atria. Conduction velocities during normal pacing were not different between groups. However, the MR LA showed increased conduction heterogeneity during pacing at short cycle lengths and during premature extrastimuli, which frequently caused pronounced regional conduction slowing. Conduction in the MR LA during extrastimulation also displayed a marked dependence on propagation direction. These phenomena were not observed in the MR RA and in control and RAP atria. Thus both models form distinctly different AF substrates; in RAP dogs, the decrease in APD(80) may stabilize reentry. In MR dogs, regional LA conduction slowing and increased directional dependency, allowing unidirectional conduction block and preferential paths of conduction, may account for increased AF inducibility.     

Age-related sensitivity to nicotine for inducible atrial tachycardia and atrial fibrillation

The influence of nicotine in modulating vulnerability to atrial tachycardia and fibrillation (AT/AF) remains ill defined. The isolated hearts of six young (2-3 mo) and six old (22-24 mo) male Fischer 344 rats were Langendorff perfused at 5 ml/min with oxygenated Tyrode solution at 37 degrees C, and the whole heart was also super-fused with warmed oxygenated Tyrode solution at 15 ml/min. Nicotine prolonged the interatrial conduction time and effective refractory period that were significantly (P < 0.05) higher in the old than in the young rats in a concentration-dependent manner. Nicotine had a biphasic effect on burst atrial pacing-induced AT in both groups, increasing it at 10-30 ng/ml while decreasing it at 50-100 ng/ml (P < 0.01). Nicotine at 10-100 ng/ml increased burst atrial pacing-induced AF in the young rats but suppressed it in the old rats (P < 0.01). Optical mapping showed the presence of multiple independent wavefronts during AF and a single periodic large wavefront during AT in both groups. Nicotine, at concentrations found in the blood of smokers (30-85 ng/ml), exerts biphasic effects on inducible AT/AF in young rats and suppresses it in the old rats by causing high degrees of interatrial conduction block.     

Percutaneous left atrial appendage closure for stroke prevention in atrial fibrillation

Background

Percutaneous left atrial appendage (LAA) closure can be an alternative to coumadin treatment in patients with atrial fibrillation (AF) at high risk for thromboembolic events and/or bleeding complications. We report the initial experience with this new technique.

Methods

Patients were eligible if they had AF with a high stroke risk (CHADS₂ score >1), and/or contraindication for coumadin therapy. The procedure was performed under general anaesthesia, using biplane fluoroscopy and (3D) transoesophageal echocardiography (TEE) guidance. Patients were discharged on coumadin until a TEE was repeated at 45 days after closure to evaluate LAA occlusion. If LAA occlusion was achieved, oral anticoagulation was discontinued and aspirin started.

Results

Percutaneous LAA closure was performed in 10 patients (50% male, age 61.6 ± 9.6 years). The median CHADS₂ score was 3 (range 2–4), median CHA₂DS₂-VASc score 3.5 (range 2–6) and HAS-BLED score 1.5 (range 1–4). Nine patients had a history of stroke and 2 patients had a history of major bleeding while on coumadin. Concomitant pulmonary vein isolation was performed in 9 patients. The device was successfully placed in all patients within a median of 56 min (38–137 min). Asymptomatic catheter thrombus occurred in one patient. At 45-day follow-up, no thromboembolic events occurred, TEE showed minimal residual flow in the LAA in three patients. In one patient the LAA device was dislocated, requiring successful percutaneous retrieval.

Conclusion

Device closure of the LAA may provide an alternative strategy to chronic coumadin therapy in patients with AF and high risk of stroke and/or bleeding complications using coumadin.     

Detection of cardiac pathologies using dimensional characteristics of RR intervals in electrocardiograms

The possibility of detecting pathologies in patients with various types of heart failure by analyzing the correlation dimension and embedding dimension of RR intervals in electrocardiograms is estimated. Limitations of the proposed approach and methods of overcoming them are discussed. It is demonstrated that these methods are suitable for provisional diagnosis.     

Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation

Background

Atrial fibrillatory cycle length has been considered one of the indices of atrial electrical remodelling during atrial fibrillation (AF), which can be assessed from surface ECG by computer-assisted calculation of atrial fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF studies since horses too, develop lone AF, however data on AF characteristics in horses are extremely sparse and non-invasive characterization of AF complexity using surface ECG processing has not been reported.

Aim

The aim was to study characteristics of induced AF and its modification by flecainide.

Methods

The study group consisted on 3 horses with spontaneous persistent AF and 13 with pace-induced AF. Seven horses were treated with saline (control) and eight with flecainide (2 mg/kg). ECGs were analysed using spatiotemporal cancellation of QRST complexes and calculation of AFR from the residual atrial signal.

Results

At AF onset, AFR was 295?±?52 fibrillations per minute (fpm) in the horses with induced AF treated with flecainide, 269?±?36 fpm in the control group (ns), and 364?±?26 fpm in the horses with spontaneous persistent AF (P?<?0.05 compared to the control group). Flecainide caused a decrease in AFR in all animals and restored sinus rhythm in the animals with induced AF. In the control animals, AFR increased from 269?±?36 fpm to a plateau of 313?±?14 fpm before decreasing to 288?±?28 fpm during the last 10% of the AF episodes preceding spontaneous conversion (P?<?0.05).

Conclusion

AFR in horses with induced AF resembles AFR in humans with paroxysmal AF. Flecainide caused a rapid decrease in AFR in all horses, further supporting the method to be a non-invasive technique to study the effect of antiarrhythmic compounds.

     

Mechano-electric feedback and atrial fibrillation

Atrial fibrillation frequently occurs under conditions associated with atrial dilatation suggesting a role of mechano-electric feedback in atrial arrhythmogenesis. Although atrial arrhythmias may be due both to abnormal focal activity and reentrant mechanisms, the majority of sustained atrial arrhythmias have been ascribed to reentrant activity. Atrial stretch may contribute to focal arrhythmias by inducing afterdepolarizations and to reentrant arrhythmias by increasing the atrial surface, by shortening the refractory period and/or slowing the conduction velocity and by increasing their spatial dispersion. Experimental and clinical studies have demonstrated that changes in mechanical loading conditions may modulate the electrophysiological properties of the atria. These studies have, for the most part, involved the effects of acute stretch on atrial refractoriness. While studies in humans and intact animals yield divergent results due to the variety of loading conditions and neurohumoral influences, experimental studies in isolated preparations clearly show that atrial refractory period and action potential duration at early levels of repolarization shorten by acute atrial dilatation. Both experimental and human studies have shown that acute atrial stretch is arrhythmogenic and may induce triggered premature beats and atrial fibrillation.     

WNT signaling in atrial fibrillation

The Wnt signaling pathway regulates physiological processes such as cell proliferation and differentiation, cell fate decisions, and stem cell maintenance and, thus, plays essential roles in embryonic development, but also in adult tissue homeostasis and repair. The Wnt signaling pathway has been associated with heart development and repair and has been shown to be crucially involved in proliferation and differentiation of progenitor cells into cardiomyocytes. The investigation of the role of the Wnt signaling pathway and the regulation of its expression/activity in atrial fibrillation has only just begun. The present minireview (I) provides original data regarding the expression of Wnt signaling components in atrial tissue of patients with atrial fibrillation or sinus rhythm and (II) summarizes the current state of knowledge of the regulation of Wnt signaling components’ expression/activity and the contribution of the various levels of the Wnt signal transduction pathway to the processes of the development, maintenance, and progression of atrial fibrillation.