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Chronic Atrial Dilation, Electrical Remodeling, and Atrial Fibrillation in the Goat

Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands

View larger version (67K): [in a new window]   Figure 1 (Top left) Relative changes in right atrium (RA) size measured during the first four weeks of total atrioventricular (AV) block. The average RA diameter was measured during five consecutive ventricular cycles from the distance between the tips of two screw-in leads (ultrasound crystals). Immediately after His bundle ablation (dotted line), the atrial diameter decreased owing to the lower ventricular rate. The size of the atria then progressively increased, resulting in 13.2 ± 3.0% dilation after four weeks of AV-block. **p < 0.01. (Top right) Time course of the increase in duration of atrial fibrillation (AF) paroxysms. In four of seven animals, the AF episodes lasted longer than 10 min after four weeks of idioventricular rhythm. (Lower panels) Photomicrographs from sections of the left atrium. A modified azan stain was used to determine cell size, and Sirius red was used to visualize collagen. After four weeks of AV block, the atrial myocytes were clearly enlarged and the amount of collagen was not increased.

View larger version (16K): [in a new window]   Figure 2 (Upper panels) Effects of 48 h of atrial fibrillation (AF) on atrial effective refractory period (AERP) in normal and dilated atria at pacing intervals between 400 and 200 ms (n = 7). In dilated atria, electrical remodeling shortened the AERP to a similar extent as in normal atria. (Lower panels) The time course of electrical remodeling (changes in AERP350) during the first 48 h of AF in normal and dilated atria. *p < 0.05; **p < 0.01; ***p < 0.001.

View larger version (15K): [in a new window]   Figure 3 (Top) Bipolar electrograms from the right atrial wall after 0, 24, and 48 h of atrial fibrillation (AF) in dilated and nondilated atria. The numbers indicate the median AF cycle length (AFCL). (Bottom) Effects of electrical remodeling on AFCL during the first 48 h of AF (n = 7). *p < 0.05.

View larger version (17K): [in a new window]   Figure 4 (Top) Example of an atrial fibrillation cycle length (AFCL) histogram in electrically remodeled atria before and after four weeks of atrioventricular (AV) block. In dilated atria the median AFCL was longer (shift to the right) and the temporal variation was higher (wider histogram). (Bottom) The absolute and relative irregularity in AFCL in seven goats. In six of seven goats the absolute and relative beat-to-beat variation in AFCL was increased after four weeks of AV block.

View larger version (23K): [in a new window]   Figure 5 Measurement of the refractory period (RPAF ) and temporal excitable gap (EGAF) during atrial fibrillation by slow fixed-rate pacing (8). After four weeks of atrioventricular block and two days of electrical remodeling, 600 stimuli with an interval of 1 s were applied to the fibrillating atria. From a bipolar electrogram close to the pacing site, the random intervals between the fibrillation waves and the stimuli (AF-S intervals) were measured together with the associated atrial fibrillation cycle length (AFCL). Capture was defined as atrial activation within 15 ms after the stimulus. The probability of local capture of the fibrillating atria followed an S-shaped curve (lower right panel). At coupling intervals of <117 ms, capture did not occur, whereas at AF-S intervals of >197 ms the atria were captured 100% of the time. The hatched columns in the lower panels indicate the range of the measured refractory periods. The AF-S interval resulting in 50% capture was taken as the RPAF (163 ms). The average temporal excitable gap was calculated by subtracting the RPAF from the median AFCL (218 – 163 ms = 55 ms).

View larger version (54K): [in a new window]   Figure 6 Fibrillation maps recorded from the free wall of the left atrium during control (left) and after four weeks of atrioventricular block (right). In dilated atria, fibrillation waves were less uniform and local crowding of isochrones occurred more frequently. Local conduction delays of >8 ms between neighboring electrodes are mapped in the lower panels. A higher degree of dissociation of fibrillation waves by lines of conduction delays was observed in dilated atria. LAA = left atrial appendage; PA = pulmonary artery.

View larger version (16K): [in a new window]   Figure 7 (Top) Percentage of local conduction delays (>8 ms/2.4 mm) and conduction block (>24 ms/2.4 mm) in the right atrial (RA) and left atrial (RA) walls of six control and seven atrioventricular (AV)-blocked goats. In dilated atria, conduction disturbances during atrial fibrillation were about twice as frequent as in non-dilated atria. (Bottom) The amount of intra-atrial conduction delay and block plotted against the mean atrial cell length in the control group (n = 6; filled circles) and in seven goats with chronic AV block (open circles). A moderate but statistically significant correlation was found between atrial cell size and intra-atrial conduction block (r = 0.60; p = 0.03).