Cardiac Sympathetic Denervation Suppresses Atrial Fibrillation and Blood Pressure in a Chronic Intermittent Hypoxia Rat Model of Obstructive Sleep Apnea

Figures

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  Figure 1. A, BW was significantly increased in every group at the end of study; B, Average postapnea BW of the CIH and CIH+CSD rats were reduced compared with the sham and CSD rats. C, No significant differences of HW among the 4 groups were found. D, HW/BW ratio was increased in the CIH and CIH+CSD rats compared with the sham and CSD rats post apnea. BW indicates body weight; CIH, chronic intermittent hypoxia group; CIH+CSD, chronic intermittent hypoxia with cardiac sympathetic denervation group; CSD, cardiac sympathetic denervation group; HW, heart weight; Postapnea, at the end of study; Sham, sham group.

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  Figure 2. Light microscopic photographs of heart slice (original magnification ×20). HE staining showed that cardiomyocytes were disarrayed with some edema and necrosis, and cardiac structural integrity was compromised with bending cardiac fibers in CIH rats. CIH indicates chronic intermittent hypoxia; CIH+CSD, chronic intermittent hypoxia with cardiac sympathetic denervation group; HE, hematoxylin and eosin staining; Sham, sham group.

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  Figure 3. Ultrasonography shows the images of the RAD and LAD. A, CIH produced statistically significant RAD dilation, and CSD treatment significantly decreased the RAD dilation. B, LAD was significantly increased after CIH, and LAD was reduced by CSD treatment. CIH indicates chronic intermittent hypoxia; CIH+CSD, chronic intermittent hypoxia with cardiac sympathetic denervation group; CSD, cardiac sympathetic denervation; LAD, left atrial diameter; RAD, right atrial diameter; Sham, sham group.

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  Figure 4. Ultrasonography shows the images of the 4 groups. CIH caused LV hypertrophy and remodeling. EF and FS were significantly decreased after CIH exposure, but CSD treatment increased the FS and EF. CIH indicates chronic intermittent hypoxia; CIH+CSD, chronic intermittent hypoxia with cardiac sympathetic denervation group; CSD, cardiac sympathetic denervation; EF, ejection fraction; FS, fractional shortening; IVSd, the intervernicular septum in diastole; IVSs, the intervernicular septum in systole; LV, left ventricle; LVIDd, left ventricular internal diameter in diastole; LVIDs, left ventricular internal diameter in systole; LVPWd, the left ventricle posterior wall in diastole; LVPWs, the left ventricle posterior wall in systole.

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  Figure 5. AF susceptibility changes post apnea. Examples of burst pacing‐induced atrial fibrillation (AF) of CIH rats (B) and failure to induce AF in a sham rat (A). AF duration (C) and AF inducibility (D) of the 4 groups. AF indicates atrial fibrillation; CIH, chronic intermittent hypoxia; CIH+CSD, chronic intermittent hypoxia with cardiac sympathetic denervation group; CSD, cardiac sympathetic denervation; SR, sinus rhythm.

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  Figure 6. Representative immunohistochemical staining of TH on the LA (A) and RA (B) among 4 groups. Red arrows indicate tyrosine hydroxylase positive nerves (original magnification ×20). C, Quantitative analysis of TH‐positive cell expression in LA of each group. D, Quantitative analysis of TH‐positive cell expression in RA of each group. CIH indicates chronic intermittent hypoxia; CIH+CSD, chronic intermittent hypoxia with cardiac sympathetic denervation group; CSD, cardiac sympathetic denervation; LA, left atrial; RA, right atrial; Sham, sham group; TH, tyrosine hydroxylase.

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  Figure 7. Representative western blot analysis shows the protein expression of Cx43 among 4 groups. A, The expression of Cx43 protein was detected by western blots. Cx43 is specifically downregulated after CIH and CSD treatment increases Cx43 expression. GAPDH was used as an internal control. B, Quantification of the total Cx43 protein expression of the 4 groups. CIH indicates chronic intermittent hypoxia; CIH+CSD, chronic intermittent hypoxia with cardiac sympathetic denervation group; CSD, cardiac sympathetic denervation; Cx43, connexin 43.

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  Figure 8. Representative immunohistochemical staining and double immunofluorescent staining of Cx43 of the 4 groups. A, Representative immunohistochemical staining of Cx43 of the 4 groups. Red arrows indicate Cx43 expression (original magnification ×20). B, Quantitative analysis of Cx43 positive cells of 4 groups. C, Examples of Cx43 (green) with α‐actinin (red) staining (original magnification ×100). D, Quantitative analysis of cardiomyocyte‐positive cells expressing Cx43 (%) in each group. CIH indicates chronic intermittent hypoxia; CIH+CSD, chronic intermittent hypoxia with cardiac sympathetic denervation group; CSD, cardiac sympathetic denervation; Cx43, connexin 43; Sham, sham group.

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  Figure 9. Double immunofluorescent staining of Cx43 (red) and β‐catenin (green) antibodies (intercalated disk associated protein) in cardiac sympathetic denervation (CSD) group. The colocalizations of Cx43 with β‐catenin (yellow) were observed at the membrane in cardiomyocytes (original magnification ×40/100). Cx43 indicates connexin 43.