. Structural atrial remodeling alters the substrate and spatiotemporal organization of atrial fibrillation: a comparison in canine models of structural and electrical atrial remodeling. Am J Physiol Heart Circ Physiol 291: H2911-H2923, 2006. First published July 28, 2006 doi:10.1152/ajpheart.01128.2005.-Several animal models of atrial fibrillation (AF) have been developed that demonstrate either atrial structural remodeling or atrial electrical remodeling, but the characteristics and spatiotemporal organization of the AF between the models have not been compared. Thirty-nine dogs were divided into five groups: rapid atrial pacing (RAP), chronic mitral regurgitation (MR), congestive heart failure (CHF), methylcholine (Meth), and control. Right and left atria (RA and LA, respectively) were simultaneously mapped during episodes of AF in each animal using highdensity (240 electrodes) epicardial arrays. Multiple 30-s AF epochs were recorded in each dog. Fast Fourier transform was calculated every 1 s over a sliding 2-s window, and dominant frequency (DF) was determined. Stable, discrete, high-frequency areas were seen in none of the RAP or control dogs, four of nine MR dogs, four of six CHF dogs, and seven of nine Meth dogs in either the RA or LA or both. Average DFs in the Meth model were significantly greater than in all other models in both LA and RA except LA DFs in the RAP model. The RAP model was the only one with a consistent LA-to-RA DF gradient (9.5 Ϯ 0.2 vs. 8.3 Ϯ 0.3 Hz, P Ͻ 0.00005). The Meth model had a higher spatial and temporal variance of DFs and lower measured organization levels compared with the other AF models, and it was the only model to show a linear relationship between the highest DF and dispersion (R 2 ϭ 0.86). These data indicate that structural remodeling of atria (models known to have predominantly altered conduction) leads to an AF characterized by a stable highfrequency area, whereas electrical remodeling of atria (models known to have predominantly shortened refractoriness without significant conduction abnormalities) leads to an AF characterized by multiple high-frequency areas and multiple wavelets. Fourier analysis; mapping; arrhythmia; electrophysiology ATRIAL FIBRILLATION (AF) is a common arrhythmia that is associated with varied underlying structural heart diseases or can be idiopathic. Because of the variety of clinical settings in which AF occurs, several animal models have been developed to study the pathophysiology of AF in each setting (10,17,20,25,27,36,40,43,44). Although AF occurs in each of the animal models, the atrial substrate of the AF appears to be different among the animal models. For example, the rapid atrial pacing (RAP) and methylcholine (Meth) models have been shown to be dominated by atrial electrical remodeling, which includes a shortening of the atrial refractoriness without atrial structural changes or changes in conduction (25,36,42). In contrast, the mitral regurgitation (MR) and congestive heart failure (CHF) models do not appear to have significant ...

Background-Much of the research performed studying the mechanism of ventricular fibrillation (VF) has been in normal ventricles rather than under a pathological condition predisposing to VF. We hypothesized that different ventricular substrates would alter the mechanism and characteristics of VF. Methods and Results-Three groups of dogs were studied: (1) control (nϭ8), (2) pacing-induced congestive heart failure (nϭ7), and (3) acute ischemia produced by 30 minutes of mid left anterior descending artery ligation (nϭ5). A noncontact mapping catheter (Ensite 3000, ESI) was placed via transseptal into the left ventricle (LV), along with an electrophysiology catheter. A multielectrode basket catheter (EP Technologies) was placed in the right ventricle, along with an electrophysiology catheter. Several episodes of VF were recorded in each animal. In addition to constructing isopotential and isochronal maps of the VF episodes, signals underwent frequency domain analysis as a fast Fourier transform was performed over a 2-second window every 1 second. From the fast Fourier transform, the dominant frequency was determined, and the organization was calculated. In control dogs, meandering, reentrant spiral wave activity was the main feature of the VF. The congestive heart failure group showed evidence of a stable rotor (nϭ3), evidence of a focal source (nϭ3), or no evidence of a driver in the LV (nϭ1). The ischemic group showed evidence of an initial focal mechanism that transitioned into reentry. In the control and ischemic groups, the LV always had higher dominant frequencies than the right ventricle. Conclusions-Different ventricular substrates produced by the different animal models altered the characteristics of VF.Thus, different mechanisms of VF may be present in the LV, depending on the animal model.

Atrial conduction properties have been shown to differ among animal atrial fibrillation (AF) models of rapid atrial pacing (RAP), chronic mitral regurgitation (MR), and control. We hypothesized that these conduction differences would continue with the onset of AF, which would affect AF spatiotemporal organization, resulting in model-specific characteristics of AF. With frequency domain analysis of electrograms acquired from high-density optical mapping, AF from the right (RA) and left (LA) atrium in animals with RAP and MR were compared with control animals. At follow-up, the hearts were excised and perfused, and optical action potentials were recorded from a 2 x 2-cm area each of the RA and LA free wall with a 16 x 16 photodiode array. AF was induced with extra stimuli, several 2.4-s AF episodes were recorded in each dog, and a fast Fourier transform was calculated. The dominant frequency (DF) was determined, and the organization (organization index, OI) was calculated as the ratio of the area under the dominant peak and its harmonics to the total area of the spectrum. All possible pairs of electrograms for each episode were cross-correlated. LA AF in the chronic MR model showed an increase in the highest DF, the number of DF domains, and in frequency gradient compared with AF in control or RAP models. In addition, there was a decrease in OI and in the correlation coefficients in the LA of the MR model. These results suggest that the AF substrate in the MR model may be different from that of control or RAP models.

No abstract