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    • Fig D illustrates a long lasting and relatively stable

    2019-06-06

    Fig. 4D illustrates a long-lasting and relatively stable rotor with a stationary PS trajectory after perfusion of ryanodine (10μM), which was used to abolish triggered activity in the setting of ACS. Taken together, these results indicate that in the presence of ACS, SRAF is governed by an evolving interplay between reentry and spontaneous focal discharges.
    Role of atrial anatomical structure in scroll wave dynamics in persistent AF Previous studies [53–55] have suggested that atrial pectinate muscle ridges could be the site of conduction delays, wavebreaks, and reentry initiation. Computer simulations have shown that wavebreak and scroll wave dynamics are affected by anatomical factors such as myocardial thickness and fiber direction [37–39]. Furthermore, in various experimental models and in humans, it was clearly demonstrated that both ionic and structural remodeling lead to AF nae inhibitor and maintenance [4,5,56,57]. In addition, recent studies [58,59] have suggested that prolonged atrial tachypacing increases interstitial fibrosis and enhances endocardial–epicardial electrical dissociation, resulting in AF perpetuation. We explored the roles of atrial structure in controlling the dynamics of persistent AF (PtAF; average duration: 21.3±11.9 day) induced in sheep by prolonged intermittent atrial tachypacing [26] (20Hz in 30-s periods) for 1–7 weeks. The LA was significantly dilated from 24.7±0.2mm in controls to 30.7±0.6mm in remodeled hearts (p<0.05). Optical imaging was carried out during acute SRAF induced in isolated hearts from PtAF animals. To reveal in detail the relationship between the atrial anatomical structure and the location of rotors and PSs, simultaneous recordings were performed from the LAA endocardium and epicardium, the RAA, and the PLA by using 3 CCD cameras and a steerable cardio-endoscope. We evaluated and classified the activation patterns at the region showing DFmax in the LAA. The vast majority of LAA patterns included I-shaped filament scroll waves (31/42 AF waves, n=5) in PtAF hearts, while centrifugal breakthroughs (19/43 AF waves) and spatiotemporal organized wavefronts (13/43 AF waves) were the most frequent in hearts without PtAF (n=5). Fig. 5A shows a representative example of a 3-D atrial scroll wave with an I-shaped filament during SRAF in a heart with PtAF. Four consecutive phase movie snapshots were superimposed with the corresponding high-resolution anatomical pictures. These 3-D scroll waves that span the LA wall from epicardium to endocardium are surprisingly stable. Fig. 5B shows the tracing of the I-shaped filament trajectory. White lines on the epicardium and endocardium indicate the trajectory of PSs. From 20–64ms, the filament remained anchored to thin myocardium bordered by thick pectinate muscles. Between 64 and 140ms, the filament drifted across a pectinate muscle segment before anchoring to a neighboring island of thin myocardium. Taken together, these 3-D scroll waves that maintained SRAF were confined to specific anatomical structures in remodeled hearts with PtAF. We compared the dynamics of rotors in 4 different settings: AF induced in the presence or absence of acute atrial stretch in normal (NH) or remodeled hearts with PtAF. In this series of experiments, AF was induced at an IAP of 12cm H2O (stretch, S) or 5cm H2O (non-stretch, NS). Fig. 6A demonstrates an example of representative phase maps and the trajectories of PSs in AF episodes with and without stretch in a heart with PtAF. In PtAF with stretch (top), a long-lasting rotor with stationary PS trajectory showing minimal drift was observed, whereas a rotor in PtAF without stretch (bottom) showed prominent drift; it appeared at the right upper corner of the LAA and quickly drifted to far region before disappearing from the field of view. Fig. 6B summarizes the rotor dynamics in 4 settings. The drifting distance of the rotor core in PtAF with stretch (S) was significantly lower compared with NH with stretch (S) and PtAF without stretch (NS). Moreover, the number of rotations in PtAF with stretch (S) was significantly higher compared with that of the other groups.