Carotid baroreceptor stimulation suppresses ventricular fibrillation in canines with chronic heart failure
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Carotid baroreceptor stimulation (CBS) has been shown to improve cardiac dysfunction and pathological structure remodelling. This study aimed to investigate the effects of CBS on the ventricular electrophysiological properties in canines with chronic heart failure (CHF). Thirty-eight beagles were randomized into control (CON), CHF, low-level CBS (LL-CBS), and moderate-level CBS (ML-CBS) groups. The CHF model was established with 6 weeks of rapid right ventricular pacing (RVP), and concomitant LL-CBS and ML-CBS were applied in the LL-CBS and ML-CBS groups, respectively. After 6 weeks of RVP, ventricular electrophysiological parameters and left stellate ganglion (LSG) neural activity and function were measured. Autonomic neural remodelling in the LSG and left ventricle (LV) and ionic remodelling in the LV were detected. Compared with the CHF group, both LL-CBS and ML-CBS decreased spatial dispersion of action potential duration (APD), suppressed APD alternans, reduced ventricular fibrillation (VF) inducibility, and inhibited enhanced LSG neural discharge and function. Only ML-CBS significantly inhibited ventricular repolarization prolongation and increased the VF threshold. Moreover, ML-CBS inhibited the increase in growth-associated protein-43 and tyrosine hydroxylase-positive nerve fibre densities in LV, increased acetylcholinesterase protein expression in LSG, and decreased nerve growth factor protein expression in LSG and LV. Chronic RVP resulted in a remarkable reduction in protein expression encoding both potassium and L-type calcium currents; these changes were partly amended by ML-CBS and LL-CBS. In conclusion, CBS suppresses VF in CHF canines, potentially by modulating autonomic nerve and ion channels. In addition, the effects of ML-CBS on ventricular electrophysiological properties, autonomic remodelling, and ionic remodelling were superior to those of LL-CBS.
KeywordsCarotid baroreceptor stimulation Ventricular arrhythmias Left stellate ganglion Autonomic remodelling Ionic remodelling
The authors are grateful for kind support from Dan Hu1,2,3, Yanhong Tang1,2,3, Xi Wang1,2,3 and Teng Wang1,2,3 (1Renmin Hospital of Wuhan University; 2Cardiovascular Research Institute, Wuhan University; 3Hubei Key Laboratory of Cardiology, Wuhan, China). This work was supported by the National Natural Science Foundation of China [Grant numbers 81570460, 81770507, 81700443]; the Health and Family Planning Commission Key Support Project of Hubei Province [Grant number WJ2017Z003], and the Fundamental Research Funds for the Central Universities [Grant number 2042017kf0064].
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- 1.Aflaki M, Qi XY, Xiao L, Ordog B, Tadevosyan A, Luo X, Maguy A, Shi Y, Tardif JC, Nattel S (2014) Exchange protein directly activated by cAMP mediates slow delayed-rectifier current remodeling by sustained beta-adrenergic activation in guinea pig hearts. Circ Res 114:993–1003. https://doi.org/10.1161/CIRCRESAHA.113.302982 CrossRefPubMedGoogle Scholar
- 4.Bourke T, Vaseghi M, Michowitz Y, Sankhla V, Shah M, Swapna N, Boyle NG, Mahajan A, Narasimhan C, Lokhandwala Y, Shivkumar K (2010) Neuraxial modulation for refractory ventricular arrhythmias. Circulation 121:2255–2262. https://doi.org/10.1161/CIRCULATIONAHA.109.929703 CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Dai M, Bao M, Zhang Y, Yu L, Cao Q, Tang Y, Huang H, Wang X, Hu D, Huang C (2016) Low-level carotid baroreflex stimulation suppresses atrial fibrillation by inhibiting left stellate ganglion activity in an acute canine model. Heart Rhythm 13:2203–2212. https://doi.org/10.1016/j.hrthm.2016.08.021 CrossRefPubMedGoogle Scholar
- 18.Koumi S, Backer CL, Arentzen CE, Sato R (1995) beta-Adrenergic modulation of the inwardly rectifying potassium channel in isolated human ventricular myocytes. Alteration in channel response to beta-adrenergic stimulation in failing human hearts. J Clin Invest 96:2870–2881. https://doi.org/10.1172/JCI118358 CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Kober L, Thune JJ, Nielsen JC, Haarbo J, Videbaek L, Korup E, Jensen G, Hildebrandt P, Steffensen FH, Bruun NE, Eiskjaer H, Brandes A, Thogersen AM, Gustafsson F, Egstrup K, Videbaek R, Hassager C, Svendsen JH, Hofsten DE, Torp-Pedersen C, Pehrson S (2016) Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med 375:1221–1230. https://doi.org/10.1056/NEJMoa1608029 CrossRefPubMedGoogle Scholar
- 20.La Rovere MT, Bigger JJ, Marcus FI, Mortara A, Schwartz PJ (1998) Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet 351:478–484. https://doi.org/10.1016/s0140-6736(97)11144-8 CrossRefPubMedGoogle Scholar
- 23.Lip GYH, Heinzel FR, Gaita F, Juanatey JRG, Le Heuzey JY, Potpara T, Svendsen JH, Vos MA, Anker SD, Coats AJ, Haverkamp W, Manolis AS, Chung MK, Sanders P, Pieske B (2015) European Heart Rhythm Association/Heart Failure Association joint consensus document on arrhythmias in heart failure, endorsed by the Heart Rhythm Society and the Asia Pacific Heart Rhythm Society. Eur J Heart Fail 17:848–874. https://doi.org/10.1002/ejhf.338/full CrossRefPubMedGoogle Scholar
- 24.Lohmeier TE, Irwin ED, Rossing MA, Serdar DJ, Kieval RS (2004) Prolonged activation of the baroreflex produces sustained hypotension. Hypertension 43:306–311. https://doi.org/10.1161/HYPERTENSIONAHA.107.087874 CrossRefPubMedGoogle Scholar
- 33.Shen MJ, Hao-Che C, Park HW, George AA, Chang PC, Zheng Z, Lin SF, Shen C, Chen LS, Chen Z, Fishbein hMC, Chiamvimonvat N, Chen PS (2013) Low-level vagus nerve stimulation upregulates small conductance calcium-activated potassium channels in the stellate ganglion. Heart Rhythm 10:910–915. https://doi.org/10.1016/j.hrthm.2013.01.029 CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Shen MJ, Shinohara T, Park HW, Frick K, Ice DS, Choi EK, Han S, Maruyama M, Sharma R, Shen C, Fishbein MC, Chen LS, Lopshire JC, Zipes DP, Lin SF, Chen PS (2011) Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines. Circulation 123:2204–2212. https://doi.org/10.1161/CIRCULATIONAHA.111.018028 CrossRefPubMedPubMedCentralGoogle Scholar
- 36.Swissa M, Zhou S, Gonzalez-Gomez I, Chang C, Lai AC, Cates AW, Fishbein MC, Karagueuzian HS, Chen P, Chen LS (2004) Long-term subthreshold electrical stimulation of the left stellate ganglion and a canine model of sudden cardiac death. J Am Coll Cardiol 43:858–864. https://doi.org/10.1016/j.jacc.2003.07.053 CrossRefPubMedGoogle Scholar
- 40.Tsuji Y, Opthof T, Kamiya K, Yasui K, Liu W, Lu Z, Kodama I (2000) Pacing-induced heart failure causes a reduction of delayed rectifier potassium currents along with decreases in calcium and transient outward currents in rabbit ventricle. Cardiovasc Res 48:300–309. https://doi.org/10.1016/S0008-6363(00)00180-2 CrossRefPubMedGoogle Scholar
- 43.Wang J, Yu Q, Dai M, Zhang Y, Cao Q, Luo Q, Tan T, Zhou Y, Shu L, Bao M (2019) Carotid baroreceptor stimulation improves cardiac performance and reverses ventricular remodelling in canines with pacing-induced heart failure. Life Sci 222:13–21. https://doi.org/10.1016/j.lfs.2019.02.047 CrossRefPubMedGoogle Scholar
- 45.Yu L, Huang B, Po SS, Tan T, Wang M, Zhou L, Meng G, Yuan S, Zhou X, Li X, Wang Z, Wang S, Jiang H (2017) Low-level tragus stimulation for the treatment of ischemia and reperfusion injury in patients with st-segment elevation myocardial infarction: a proof-of-concept study. JACC Cardiovasc Interv 10:1511–1520. https://doi.org/10.1016/j.jcin.2017.04.036 CrossRefPubMedGoogle Scholar
- 47.Zheng C, Li M, Inagaki M, Kawada T, Sunagawa K, Sugimachi M (2005) Vagal stimulation markedly suppresses arrhythmias in conscious rats with chronic heart failure after myocardial infarction. Conf Proc IEEE Eng Med Biol Soc 7:7072–7075. https://doi.org/10.1109/IEMBS.2005.1616135 CrossRefPubMedGoogle Scholar