Effects of Renal Denervation via Renal Artery Adventitial Cryoablation on Atrial Fibrillation and Cardiac Neural Remodeling

Wei Wang, Zhaolei Jiang, Rongxin Lu, Hao Liu, Nan Ma, Jie Cai, Min Tang, Ju Mei, Wei Wang, Zhaolei Jiang, Rongxin Lu, Hao Liu, Nan Ma, Jie Cai, Min Tang, Ju Mei

Abstract

Introduction: Catheter-based renal denervation (RDN) could reduce cardiac sympathetic nerve activity (SNA) and inhibit atrial fibrillation (AF). However, the reliability is uncertain, because the renal sympathetic nerves are mainly distributed in the adventitial surface of the renal artery.

Objective: The aims of this study were to test the hypothesis that renal artery adventitial ablation (RAAA) definitely had the effects of RDN and to study the effects of RDN via renal artery adventitial cryoablation (RAAC) on AF and cardiac neural remodeling.

Methods: Twenty beagle canines were randomly assigned to two groups: the left RDN group (LRDN, n=10), which underwent left RDN via RAAC; the Sham group (n=10). After 2 months of postoperative recovery, AF vulnerability, AF duration, and histological examination were performed in both groups.

Results: Compared with the Sham group, left stellate ganglion (LSG) tissue fibrosis was increased in the LRDN group. LRDN significantly increased the percentage of TH-negative ganglionic cells and decreased the density of TH-positive nerves in the LSG (P < 0.001). Also, the densities of TH-positive nerves and GAP43 immunoreactivity within the left atrium (LA) were significantly decreased in the LRDN group (P < 0.05). After LA burst pacing, all 10 canines (100%) could be induced AF in the Sham group, but only 4 of 10 canines (40%) could be induced AF in the LRDN group (P=0.011). The percentage of LA burst stimulation with induced AF was 26.7% (8/30) in the LRDN group, which was significantly decreased compared with that of the Sham group (53.3%, 16/30) (P=0.035). In addition, AF duration was also significantly decreased in the LRDN group (13.3 ± 5.1 s) compared with that of the Sham group (20.3 ± 7.3 s, P=0.024).

Conclusions: RDN via RAAC could cause cardiac neural remodeling and effectively inhibit AF inducibility and shorten AF duration. It may be useful in selecting therapeutic approaches for AF patients.

Figures

Figure 1
Figure 1
Renal artery ablation. (a) Renal artery adventitial cryoablation (RAAC). (b) Morphological changes of the LRA after LRDN. DR: damage region; NR: normal region.
Figure 2
Figure 2
Masson trichrome staining of LSG. (a) and (b): Tissue fibrosis seen at low magnification in Sham group; (c) and (d): Tissue fibrosis seen at high magnification in LRDN group.
Figure 3
Figure 3
Tyrosine hydroxylase (TH) immunostaining of LSG. (a) TH staining showed TH-negative ganglion cells (red arrows) and TH-positive ganglion cells in LSG in Sham group; (b) TH staining showed TH-negative ganglion cells (red arrows) and TH-positive ganglion cells in LSG in LRDN group.
Figure 4
Figure 4
Immunostaining results in LSG or LA between Sham group and LRDN group. (a) The percentage of TH-negative ganglionic cells in LSG in both Sham group and LRDN group; (b) comparison between the density of TH-positive nerves in LSG between Sham group and LRDN group; (c) the density of TH-positive nerves in LA in both Sham group and LRDN group; (d) comparison between the density of GAP43-positive nerves in LA between Sham group and LRDN group (∗P < 0.05 vs. the Sham group; ∗∗P < 0.01 vs. the Sham group).
Figure 5
Figure 5
TH and GAP43 immunostaining of LA. (a) TH staining showed the densities of TH-positive nerves (brown) within the LA in Sham group; (b) TH staining showed the densities of TH-positive nerves within the LA in LRDN group; (c) GAP43 staining showed the density of GAP43 immunoreactivity in the LA in Sham group; (d) GAP43 staining showed the density of GAP43 immunoreactivity in the LA in LRDN group.
Figure 6
Figure 6
AF inducibility and AF duration between Sham group and LRDN group. (a) The percentage of canines with induced AF in LSG in both Sham group and LRDN group; (b) comparison between the percentage of stimulations with induced AF between Sham group and LRDN group; (c) comparison between the AF duration between Sham group and LRDN group (∗P < 0.05 vs. the Sham group).

References

    1. Guo Y., Tian Y., Wang H., Si Q., Wang Y., Lip G. Y. H. Prevalence, incidence, and lifetime risk of atrial fibrillation in China: new insights into the global burden of atrial fibrillation. Chest. 2015;147(1):109–119. doi: 10.1378/chest.14-0321.
    1. Shen M. J., Zipes D. P. Role of the autonomic nervous system in modulating cardiac arrhythmias. Circulation Research. 2014;114(6):1004–1021. doi: 10.1161/circresaha.113.302549.
    1. Shen M. J., Choi E. K., Tan A. Y., et al. Neural mechanisms of atrial arrhythmias. Nature Reviews Cardiology. 2011;9(1):30–39. doi: 10.1038/nrcardio.2011.139.
    1. Jayachandran J. V., Sih H. J., Winkle W., Zipes D. P., Hutchins G. D., Olgin J. E. Atrial fibrillation produced by prolonged rapid atrial pacing is associated with heterogeneous changes in atrialsympathetic innervation. Circulation. 2000;101(10):1185–1191. doi: 10.1161/01.cir.101.10.1185.
    1. Linz D., van Hunnik A., Hohl M., et al. Catheter-based renal denervation reduces atrial nerve sprouting and complexity of atrial fibrillation in goats. Circulation: Arrhythmia and Electrophysiology. 2015;8(2):466–474. doi: 10.1161/circep.114.002453.
    1. Wang X., Huang C., Zhao Q., et al. Effect of renal sympathetic denervation on the progression of paroxysmal atrial fibrillation in canines with long-term intermittent atrial pacing. Europace. 2015;17(4):647–654. doi: 10.1093/europace/euu212.
    1. Zhou Q., Zhou X., TuEr-Hong Z. L., et al. Renal sympathetic denervation suppresses atrial fibrillation induced by acute atrial ischemia/infarction through inhibition of cardiac sympathetic activity. International Journal of Cardiology. 2016;203:187–195. doi: 10.1016/j.ijcard.2015.10.120.
    1. Bhatt D. L., Kandzari D. E., O’Neill W. W., et al. A controlled trial of renal denervation for resistant hypertension. New England Journal of Medicine. 2014;370(15):1393–1401. doi: 10.1056/nejmoa1402670.
    1. Atherton D. S., Deep N. L., Mendelsohn F. O. Micro-anatomy of the renal sympathetic nervous system: a human postmortem histologic study. Clinical Anatomy. 2012;25(5):628–633. doi: 10.1002/ca.21280.
    1. Chen P. S., Chen L. S., Fishbein M. C., Lin S. F., Nattel S. Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy. Circulation Research. 2014;114(9):1500–1515. doi: 10.1161/circresaha.114.303772.
    1. Hellyer J., Akingba A., Rhee K. S., et al. Autonomic nerve activity and blood pressure in ambulatory dogs. Heart Rhythm. 2013;11(2):307–313. doi: 10.1016/j.hrthm.2013.11.022.
    1. Choi E. K., Shen M. J., Han S., et al. Intrinsic cardiac nerve activity and paroxysmal atrial tachyarrhythmia in ambulatory dogs. Circulation. 2010;121(24):2615–2623. doi: 10.1161/circulationaha.109.919829.
    1. Chen M., Yu L., Zhou X., Liu Q., Jiang H., Zhou S. Low-level vagus nerve stimulation: an important therapeutic option for atrial fibrillation treatment via modulating cardiac autonomic tone. International Journal of Cardiology. 2015;199:437–438. doi: 10.1016/j.ijcard.2015.07.083.
    1. Hou Y., Zhou Q., Po S. S. Neuromodulation for cardiac arrhythmia. Heart Rhythm. 2016;13(2):584–592. doi: 10.1016/j.hrthm.2015.10.001.
    1. Shen M. J., Shinohara T., Park H. W., et al. Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines. Circulation. 2011;123(20):2204–2212. doi: 10.1161/circulationaha.111.018028.
    1. Driessen A. H. G., Berger W. R., Krul S. P. J., et al. Ganglion plexus ablation in advanced atrial fibrillation: the AFACT study. Journal of the American College of Cardiology. 2016;68(11):1155–1165. doi: 10.1016/j.jacc.2016.06.036.
    1. Jiang Z., Yin H., He Y., et al. Efficacy and safety of novel epicardial circumferential left atrial ablation with pulmonary vein isolation in sustained atrial fibrillation. Heart Vessels. 2015;30(5):675–681. doi: 10.1007/s00380-014-0594-4.
    1. Giannopoulos G., Kossyvakis C., Angelidis C., et al. Coincidental ganglionated plexus modification during radiofrequency pulmonary vein isolation and post-ablation arrhythmia recurrence. Europace. 2017;19(12):1967–1972. doi: 10.1093/europace/euw309.
    1. Nishida K., Datino T., Macle L., Nattel S. Atrial fibrillation ablation: translating basic mechanistic insights to the patient. Journal of the American College of Cardiology. 2014;64(8):823–831. doi: 10.1016/j.jacc.2014.06.1172.
    1. Zheng S., Zeng Y., Li Y., Han J., Zhang H., Meng X. Active ganglionated plexi is a predictor of atrial fibrillation recurrence after minimally invasive surgical ablation. Journal of Cardiac Surgery. 2014;29(2):279–285. doi: 10.1111/jocs.12299.
    1. Nammas W., Airaksinen J. K., Paana T., Karjalainen P. P. Renal sympathetic denervation for treatment of patients with atrial fibrillation: reappraisal of the available evidence. Heart Rhythm. 2016;13(12):2388–2394. doi: 10.1016/j.hrthm.2016.08.043.
    1. Yu L., Huang B., Wang Z., et al. Impacts of renal sympathetic activation on atrial fibrillation: the potential role of the autonomic cross talk between kidney and heart. Journal of the American Heart Association. 2017;6(3) doi: 10.1161/jaha.116.004716.e004716
    1. Huang B., Yu L., Scherlag B. J., et al. Left renal nerves stimulation facilitates ischemia-induced ventricular arrhythmia by increasing nerve activity of left stellate ganglion. Journal of Cardiovascular Electrophysiology. 2014;25(11):1249–1256. doi: 10.1111/jce.12498.
    1. Tsai W.-C., Yi-Hsin C., Chinda K., et al. Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs. Heart Rhythm. 2017;14(2):255–262. doi: 10.1016/j.hrthm.2016.10.003.
    1. Jiang Z., Zhao Y., Doytchinova A., et al. Using skin sympathetic nerve activity to estimate stellate ganglion nerve activity in dogs. Heart Rhythm. 2015;12(6):1324–1332. doi: 10.1016/j.hrthm.2015.02.012.
    1. Armour J. A. Functional anatomy of intrathoracic neurons innervating the atria and ventricles. Heart Rhythm. 2010;7(7):994–996. doi: 10.1016/j.hrthm.2010.02.014.
    1. Cao J. M., Chen L. S., KenKnight B. H., et al. Nerve sprouting and sudden cardiac death. Circulation Research. 2000;86(7):816–821. doi: 10.1161/01.res.86.7.816.
    1. Nguyen B. L., Fishbein M. C., Chen L. S., Chen P. S., Masroor S. Histopathological substrate for chronic atrial fibrillation in humans. Heart Rhythm. 2009;6(4):454–460. doi: 10.1016/j.hrthm.2009.01.010.
    1. Gallo C., Bocchino P. P., Magnano M., et al. Autonomic tone activity before the onset of atrial fibrillation. Journal of Cardiovascular Electrophysiology. 2017;28(3):304–314. doi: 10.1111/jce.13150.

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