Blocking Intermediate-Conductance Calcium-Activated Potassium Channels in the Macrophages Around Ganglionated Plexi Suppresses Atrial Fibrillation Vulnerability in Canines With Rapid Atrial Pacing

Figures

• 

  FIGURE 1. Experimental flow chart. Abbreviations: BS, baseline; RAP, rapid atrium pacing; M, measurement.

• 

  FIGURE 2. ARGP activity at baseline and after rapid atrial pacing in the three groups. (A) ARGP activity at baseline, after 3 h, and after 6 h in the three groups; (B): Microelectrodes were inserted into the ARGP; (C,D) The frequency and the amplitude of ARGP in the three groups. The frequency and amplitude of ARGP activity was increased after rapid atrial pacing. TRAM-34 injection inhibited the increased ARGP activity. ***p < 0.01vs the control group and TRAM-34 group; ###p < 0.01vs the control group.

• 

  FIGURE 3. Results of electrophysiological measurements. (A–F) ERP changes at RAA, LAA, RSPV, RIPV, LSPV, and LIPV during 6-h stimulation. *p < 0.05 vs baseline (G) Mean AF duration, and (H) Mean AF inducibility changes in the Control, RAP, and TRAM-34 groups. *p < 0.05 vs baseline; # p < 0.05 vs the RAP group. Abbreviations: RAA, right atrial appendage, LAA, left atrial appendage RSPV, right superior pulmonary vein, RIPV, right inferior pulmonary vein, LSPV, left superior pulmonary vein, LIPV, left inferior pulmonary vein, ERP, effective refractory period, AF, atrial fibrillation.

• 

  FIGURE 4. Representative picture of AF induction in the three groups. In the control group, the burst pacing didn’t induce AF (A). In the TRAM-34 group, after 6 h pacing, the burst pacing didn’t induce AF (B). In the RAP group, after 6 h pacing, the burst pacing induced AF last for 21.3 s (C,D).

• 

  FIGURE 5. Levels of CD68+, iNOS, and arg1 in the ARGP in the three groups. Representative images and quantitative analysis of immunofluorescence staining for CD68+ (red) in the ARGP (A,B) (n = 6, 40X). Quantitative analysis of RT-PCR of iNOS and arg1 in ARGP (C,D). RAP increased the secretion of inflammation cytokines and promoted macrophage polarization from M2 to M1 compared to that in the control group. However, TRAM-34 can attenuate this effect. ***p < 0.01vs the control group and TRAM-34 group; ###p < 0.01vs the control group.

• 

  FIGURE 6. Levels of inflammatory cytokines in the three groups. Western blotting and quantitative analysis of IL-1β, TNF-α, and IL-6 in ARGP (A–C). ***p < 0.01 vs the control group and TRAM-34 group; ###p < 0.01vs the control group.