Re-entrant excitations are accepted as being responsible for genesis of atrial fibrillation and flutter (AF/AFL); however, detailed activation patterns of these arrhythmias are not fully elucidated with reference to the morphological correlations. We hypothesized that intrinsic regional differences in atrial structure, especially those in muscle content, can be a substrate for abnormal impulse propagation leading to generation of AF/AFL. To address this issue, we evaluated the possible re-entrant pathways on the whole atrial tissue in excised rat hearts and explored their correlations of histologic background.
By using Langendorff-perfused hearts with bilateral lungs at 32°C (11-13-week-old males, n=19), spatiotemporal patterns of excitation on the posterior surface of the di-4ANEPPS-stained whole atria (15.9x13.6mm, 188x160 pixels) were optically visualized by a high-speed CMOS camera (MiCAM02; Brainvision) at 500 frames/s. Atrial arrhythmias were induced by a premature stimulus after 5-Hz consecutive pacing at the right atrium. Following the optical imaging of atrial arrhythmias, histological analyses (n = 9) were conducted on the posterior surface of the whole atria sectioned on the short axis plane by using a digital slide scanner system (ScanScope, Aperio).
Of 19 hearts examined AF/AFL was induced in 15 hearts, most of which initially showed re-entrant excitations through the roof region of the left atrium and the coronary sinus with subsequent development of complex patterns of re-entrant propagations, i.e., meandering. The conduction velocity at the roof of the left atrium was significantly slower than that of the coronary sinus (42.4 ± 16.6 vs 53.3 ± 9.2 cm/s, p < 0.05) just before the initiation of re-entry, suggesting the existence of slow and fast conduction pathways. Quantitative histologic evaluation by Masson's trichrome staining of atrial tissues, divided into seven different areas, i.e., anterior region of the right atrium, roof region, anterior region, lateral region, and posterior region of the left atrium, septum, and coronary sinus, revealed that the myocardial density in the roof region of the left atrium was significantly lower than that in the coronary sinus (76.3 ± 2.5 vs 82.3 ± 4.7 %, p < 0.01) and the remaining atrial areas.
In summary, the combined functional and histological analyses of the rat atria enabled us to elucidate a possible morphological substrate for arrrhythmias. The observed regional differences in myocardial density between the left atrial roof and the coronary sinus may become an important substrate for AF/AFL under certain diseased conditions.