Background-High-frequency fractionated electrograms recorded during atrial fibrillation (AF) in the posterior left atrium (PLA) and elsewhere are being used as target sites for catheter ablation. We tested the hypothesis that highly periodic electric waves emerging from AF sources at or near the PLA give rise to the most fractionated activity in adjacent locations. Methods and Results-Sustained AF was induced in 8 isolated sheep hearts (0.5 mol/L acetylcholine). Endocardial videoimaging (DI-4-ANEPPS) and electric mapping of the PLA enabled spatial characterization of dominant frequencies (DFs) and a regularity index (ratio of DF to total power). Regularity index showed that fractionation was lowest within the area with the maximal DF (DFmax domain; 0.

We demonstrate for the first time that an increase in intra-atrial pressure increases the rate and organization of waves emanating from the superior pulmonary veins underlying stretch-related AF.

Tissue heterogeneities may play an important role in the mechanism of ventricular tachycardia (VT) and fibrillation (VF) and can lead to a complex spatial distribution of excitation frequencies. Here we used optical mapping and Fourier analysis to determine the distribution of excitation frequencies in >20 000 sites of fibrillating ventricular tissue. Our objective was to use such a distribution as a tool to quantify the degree of organization during VF. Fourteen episodes of VT/VF were induced via rapid pacing in 9 isolated, coronary perfused, and superfused sheep ventricular slabs (3x3 cm(2)). A dual-camera video-imaging system was used for simultaneous optical recordings from the entire epi- and endocardial surfaces. The local frequencies of excitation were determined at each pixel and displayed as dominant frequency (DF) maps. A typical DF map consisted of several (8.2+/-3.6) discrete areas (domains) with a uniform DF within each domain. The DFs in adjacent domains were often in 1:2, 3:4, or 4:5 ratios, which was shown to be a result of an intermittent Wenckebach-like conduction block at the domain boundaries. The domain patterns were relatively stable and could persist from several seconds to several minutes. The complexity in the organization of the domains, the number of domains, and the dispersion of frequencies increased with the rate of the arrhythmia. Domain patterns on the epicardial and endocardial surfaces were not correlated. Sustained epicardial or endocardial reentry was observed in only 3 episodes. Observed frequency patterns during VT/VF suggest that the underlying mechanism may be a sustained intramural reentrant source interacting with tissue heterogeneities.

Voltage-sensitive fluorescent dyes have become powerful tools for the visualization of excitation propagation in the heart. However, until recently they were used exclusively for surface recordings. Here we demonstrate the possibility of visualizing the electrical activity from inside cardiac muscle via fluorescence measurements in the transillumination mode (in which the light source and photodetector are on opposite sides of the preparation). This mode enables the detection of light escaping from layers deep within the tissue. Experiments were conducted in perfused (8 mm thick) slabs of sheep right ventricular wall stained with the voltage-sensitive dye di-4-ANEPPS. Although the amplitude and signal-to-noise ratio recorded in the transillumination mode were significantly smaller than those recorded in the epi-illumination mode, they were sufficient to reliably determine the activation sequence. Penetration depths (spatial decay constants) derived from measurements of light attenuation in cardiac muscle were 0.8 mm for excitation (520 +/- 30 nm) and 1.3 mm for emission wavelengths (640 +/- 50 nm). Estimates of emitted fluorescence based on these attenuation values in 8-mm-thick tissue suggest that 90% of the transillumination signal originates from a 4-mm-thick layer near the illuminated surface. A 69% fraction of the recorded signal originates from > or =1 mm below the surface. Transillumination recordings may be combined with endocardial and epicardial surface recordings to obtain information about three-dimensional propagation in the thickness of the myocardial wall. We show an example in which transillumination reveals an intramural reentry, undetectable in surface recordings.

The results strongly support the hypothesis that IK1 plays an important role in rotor stabilization and VF dynamics.

Abstract-Atrial fibrillation (AF) may result from stationary reentry in the left atrium (LA), with fibrillatory conduction toward the right atrium (RA). We hypothesize that periodic input to the RA at an exceedingly high frequency results in disorganized wave propagation, compatible with fibrillatory conduction. Simultaneous endocardial and epicardial optical mapping (di-4-ANEPPS) was performed in isolated, coronary-perfused sheep RA. Rhythmic pacing of Bachmann's bundle allowed well-controlled and realistic conditions for LA-driven RA. Pacing at increasingly higher frequencies (2.0 to 6.0 Hz) led to increasing delays in activation distal to major branching sites of the crista terminalis and pectinate bundles, culminating in spatially distributed intermittent blockade at or above Ϸ6.5 Hz. At this "breakdown frequency," the direction of RA propagation became completely variable from beat to beat and thus transformed into fibrillatory conduction. Such frequency-dependent changes were independent of action potential duration. Rather, the spatial boundaries between proximal and distal frequencies correlated well with branch sites of the pectinate musculature. Thus, there exists a breakdown frequency in the sheep RA below which activity is periodic throughout the atrium and above which it is fibrillation-like. The data are consistent with the ideas that during AF, high-frequency activation initiated in the LA undergoes fibrillatory conduction toward the RA, and that sink-to-source effect at branch points of the crista terminalis and pectinate muscles is important in determining the complexity of the arrhythmia. , excitation frequency in the left atrium (LA) may be higher than in the right atrium (RA), 1-5 and LA activation patterns may be spatially and temporally periodic. 6 -8 Moreover, a consistent LA-to-RA dominant frequency (DF) gradient correlates with impulse propagation from LA to RA 9,10 across interatrial pathways, such as Bachmann's bundle (BB) and the inferoposterior pathway along the anterior wall of the coronary sinus. 11 Thus, at least in some cases, AF results from activation by relatively stationary high-frequency sources of impulses, which undergo complex spatially distributed intermittent block patterns, imposed by the presence of functional and/or anatomical obstacles in their path.We sought to study rigorously and in detail the response of the RA to incoming high-frequency excitation from the LA. Specifically, we used an isolated, coronary-perfused RA preparation to quantify the frequency-dependent nature of the propagation of wavefronts entering the RA from BB 9 and the basis of fibrillatory conduction. We hypothesize that the bundle-like structure of the normal RA, with its complicated network of pectinate muscles, is a substrate for frequencydependent conduction delay and block. Our preparation provides realistic and well-controlled conditions for testing such a conjecture. By pacing BB at varying frequencies, we demonstrate that 1:1 propagation across the crista terminalis and the grid of pect...

Abstract-The mechanisms by which Naϩ -channel blocking antiarrhythmic drugs terminate atrial fibrillation (AF) remain unclear. Classical "leading-circle" theory suggests that Na ϩ -channel blockade should, if anything, promote re-entry. We used an ionically-based mathematical model of vagotonic AF to evaluate the effects of applying pure Na ϩ -current (I Na ) inhibition during sustained arrhythmia. Under control conditions, AF was maintained by 1 or 2 dominant spiral waves, with fibrillatory propagation at critical levels of action potential duration (APD) dispersion. I Na inhibition terminated AF increasingly with increasing block, terminating all AF at 65% block. During 1:1 conduction, I Na inhibition reduced APD (by 13% at 4 Hz and 60% block), conduction velocity (by 37%), and re-entry wavelength (by 24%). During AF, I Na inhibition increased the size of primary rotors and reduced re-entry rate (eg, dominant frequency decreased by 33% at 60% I Na inhibition) while decreasing generation of secondary wavelets by wavebreak. Three mechanisms contributed to I Na block-induced AF termination in the model: (1) enlargement of the center of rotation beyond the capacity of the computational substrate; (2) decreased anchoring to functional obstacles, increasing meander and extinction at boundaries; and (3) reduction in the number of secondary wavelets that could provide new primary rotors. Optical mapping in isolated sheep hearts confirmed that tetrodotoxin dose-dependently terminates AF while producing effects qualitatively like those of I Na inhibition in the mathematical model. We conclude that pure I Na inhibition terminates AF, producing activation changes consistent with previous clinical and experimental observations. These results provide insights into previously enigmatic mechanisms of class I antiarrhythmic drug-induced AF termination. The full text of this article is available online at http://circres.ahajournals.org (Circ Res. 2005;96:e35-e47.) Key Words: atrial fibrillation Ⅲ mathematical model Ⅲ class I drugs Ⅲ sodium channels C lass I antiarrhythmic drugs terminate clinical atrial fibrillation (AF), but the electrophysiological mechanisms remain poorly understood. 1 AF is generally considered to be a re-entrant arrhythmia, and the stability of AF is classically related to the wavelength. 2 The wavelength (product of refractory period and conduction velocity [CV]) is thought to represent the minimum path length for re-entry and therefore to determine the size of functional re-entry circuits. 3 The most commonly accepted mechanism for antiarrhythmic drug termination of AF is drug-induced wavelength increases that reduce the number of circuits that the atria may accommodate.Experimental evidence has been presented suggesting that class I antiarrhythmic agents act on AF by changing the effective refractory period (ERP) and the wavelength. 2,4,5 Recent data have challenged established notions of antiarrhythmic drug action by showing that potent Na ϩ -channel blockers can terminate AF without increasing the wav...

In a study involving 10 different sites, independent results of measurements of ultrasonic properties on equivalent tissue-mimicking samples are reported and compared. The properties measured were propagation speed, attenuation coefficients, and backscatter coefficients. Reasonably good agreement exists for attenuation coefficients, but less satisfactory results were found for propagation speeds. As anticipated, agreement was not impressive in the case of backscatter coefficients. Results for four sites agreed rather well in both absolute values and frequency dependence, and results from other sites were lower by as much as an order of magnitude. The study is valuable for laboratories doing quantitative studies. KEY WORDS: Measurements; Speed; Attenuation; Backscatter; Interlaboratory comparison. n 1986 an article was published to compare measurements made of ultrasonic attenuation coefficients and propagation speeds in TM phantom materials produced at the University of Wisconsin and sent to participating laboratories. 1 To assess stability of ultrasonic properties during the study, measurements were done on those phantoms at the University of Wisconsin laboratories before and after the measurements were made at other laboratories. The same type of study, involving 10 labo-