Effects of febuxostat on atrial remodeling in a rabbit model of atrial fibrillation induced by rapid atrial pacing.

Figures

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  Figure 1.. ECG recordings of rabbits during electrophysiology studies. (A): The ECG of limb leads under the normal state; (B): the ECG of limb leads and the potential of the left atrium under the normal state; (C): the ECG of limb leads during rapid atrial pacing at 600 beats/min; (D): intracardiac electrophysiological examination and S1-S2 programmed stimulation; (E): AERP measurement. S2 (stimulate interval = 65 ms) was unable to induce a propagated atrial response; and (F): representative atrial fibrillation episode induced by high-frequency atrial burst pacing at 1000 beats/min. AERP: atrial effective refractory period.

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  Figure 2.. Effects of febuxostat on atrial electrical remodeling. (A): Baseline AERP200 in the four groups; (B): AERP200 after four weeks of RAP in the four groups; (C): effects of febuxostat on the inducibility of AF; (D): quantitative analysis of the mRNA expression of Cav1.2 in the four groups; and (E): quantitative analysis of the mRNA expression of Kv4.3 in the four groups. Values are expressed as means ± SD (n = 6/group); *P < 0.05 and **P < 0.01 vs. Group S; #P < 0.05, ##P<0.01 vs. Group P; ▴P < 0.05, ▴▴P < 0.01 vs. Group LFP. Group HFP: RAP with 10 mg/kg per day febuxostat group; Group LFP: RAP with 5 mg/kg per day febuxostat group; Group P: RAP group; Group S: sham-operated group. AERP: atrial effective refractory period; AF: atrial fibrillation; NS: not significant; RAP: rapid atrial pacing.

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  Figure 3.. Effects of febuxostat on atrial structural remodeling. (A): Representative images showing H&E staining in tissues from the four groups; (B): representative images showing Masson's trichrome staining in tissues from the four groups; (C): semiquantitative analysis of the proportion of fibrous tissue area in the four groups; (D): representative transmission electron micrographs of left atrial ultrastructure in the four groups; and (E): representative echocardiographic images of the left atrium in the four groups. Values are expressed as means ± SD (n = 6 per group); **P < 0.01 vs. Group S; ##P < 0.01 vs. Group P; ▴▴P < 0.01 vs. Group LFP. Group HFP: RAP with 10 mg/kg per day febuxostat group; Group LFP: RAP with 5 mg/kg per day febuxostat group; Group P: RAP group; Group S: sham-operated group. 200 × magnification, bar = 100 µm; 400 × magnification, bar = 50 µm; 2000× magnification, bar = 50 µm; 5000 × magnification, bar = 20 µm. RAP: rapid atrial pacing.

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  Figure 4.. Effects of febuxostat on the expression of TGF-β1, Smad7, eNOS, Collagen I, and α-SMA in the left atrium. (A): Western blot analysis of the protein expression levels of TGF-β1, Smad7, eNOS, Collagen I, and α-SMA in samples from Group P, Group S, Group LFP, and Group HFP; (B): quantitative analysis of the mRNA and protein expression levels of TGF-β1; (C): quantitative analysis of the mRNA and protein expression levels of Smad7; (D): quantitative analysis of the mRNA and protein expression levels of eNOS; (E): quantitative analysis of the mRNA and protein expression levels of Collagen I; and (F): quantitative analysis of the mRNA and protein expression levels of α-SMA. Values are expressed as means ± SD (n = 6/group); *P < 0.05 and ** P <0.01 vs. Group S; #P < 0.05 and ##P < 0.01 vs. Group P; ▴P < 0.05 and ▴▴P < 0.01 vs. Group LFP. Group S: sham-operated group; Group P: RAP group; Group LFP: RAP with 5 mg/kg per day febuxostat group; Group HFP: RAP with 10 mg/kg per day febuxostat group. RAP: rapid atrial pacing.