Abstract
High thoracic epidural anesthesia (HTEA) blocks the afferent and efferent cardiac sympathetic nerve fibers and may affect atrial electrophysiological characteristics and nerve sprouting in patients with atrial fibrillation (AF). In this study, 18 dogs were randomly divided into a control group (n = 6), in which dogs were atrially paced at 400 beats/min for 6 weeks; an HTEA group (n = 6), in which dogs underwent atrial pacing and HTEA for 6 weeks; and a sham-operated group (n = 6), in which dogs underwent the operation but did not receive atrial pacing or HTEA. Electrophysiological examinations were performed in all groups. Cardiac nerves were immunocytochemically stained with anti-growth-associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. The protein expressions of nerve growth factor (NGF), GAP43 and TH in atrial myocardium were also studied by western blot. In addition, the plasma levels of C-reactive protein (CRP) and norepinephrine, as well as atrial production of superoxide anion (O ·−2 ) and malondialdehyde, were measured. In the HTEA group, atrial effective refractory period increased (P < 0.05) and AF maintenance decreased (P < 0.01) significantly compared with the control group. The densities of GAP43-positive nerves and TH-positive nerves were significantly lower in the HTEA group compared with the control group. The protein levels of NGF, GAP43 and TH were also lower in the HTEA group compared with the control group. A significant positive correlation between the expressions of NGF and GAP43 (P < 0.01) was observed. A similar correlation was demonstrated for NGF and TH (P < 0.01) in our study. Furthermore, the plasma levels of CRP and norepinephrine, as well as the amount of O ·−2 and malondialdehyde produced from myocardium, decreased in the HTEA group compared with the control group. In conclusion, HTEA inhibited electrical and nerve remodeling and reduced the maintenance of AF in a canine AF model, in which process HTEA exhibited anti-inflammatory and antioxidant effects, indicating that, in addition to the efferent cardiac sympathetic nerve, afferent fibers also play an important role in the initiation and/or maintenance of AF.
Similar content being viewed by others
References
Ahlers O, Nachtigall I, Lenze J, Goldmann A, Schulte E, Höhne C, Fritz G, Keh D (2008) Intraoperative thoracic epidural anaesthesia attenuates stress-induced immunosuppression in patients undergoing major abdominal surgery. Br J Anaesth 101:781–787. doi:10.1093/bja/aen287
Allessie M, Ausma J, Schotten U (2002) Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res 54:230–246. doi:10.1016/S0008-6363(02)00258-4
Ausma J, Wijffels M, Thoné F, Wouters L, Allessie M, Borgers M (1997) Structural changes of atrial myocardium due to sustained atrial fibrillation in the goat. Circulation 96:3157–3163
Aviles RJ, Martin DO, Apperson-Hansen C, Houghtaling PL, Rautaharju P, Kronmal RA, Tracy RP, Van Wagoner DR, Psaty BM, Lauer MS, Chung MK (2003) Inflammation as a risk factor for atrial fibrillation. Circulation 108:3006–3010. doi:10.1161/01.CIR.0000103131.70301.4F
Bakhtiary F, Therapidis P, Dzemali O, Ak K, Ackermann H, Meininger D, Kessler P, Kleine P, Moritz A, Aybek T, Dogan S (2007) Impact of high thoracic epidural anesthesia on incidence of perioperative atrial fibrillation in off-pump coronary bypass grafting: a prospective randomized study. J Thorac Cardiovasc Surg 134:460–464. doi:10.1016/j.jtcvs.2007.03.043
Berendes E, Schmidt C, Van Aken H, Hartlage MG, Wirtz S, Reinecke H, Rothenburger M, Scheld HH, Schlüter B, Brodner G, Walter M (2003) Reversible cardiac sympathectomy by high thoracic epidural anesthesia improves regional left ventricular function in patients undergoing coronary artery bypass grafting: a randomized trial. Arch Surg 138:1283–1290. doi:10.1001/archsurg.138.12.1283
Bruins P, te Velthuis H, Yazdanbakhsh AP, Jansen PG, van Hardevelt FW, de Beaumont EM, Wildevuur CR, Eijsman L, Trouwborst A, Hack CE (1997) Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia. Circulation 96:3542–3548
Carnes CA, Chung MK, Nakayama T, Nakayama H, Baliga RS, Piao S, Kanderian A, Pavia S, Hamlin RL, McCarthy PM, Bauer JA, Van Wagoner DR (2001) Ascorbate attenuates atria pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation. Circ Res 89:e32–e38. doi:10.1161/hh1801.097644
Chamberlain DP, Chamberlain BD (1986) Changes in the skin temperature of the trunk and their relationship to sympathetic blockade during spinal anesthesia. Anesthesiology 65:139–143. doi:10.1097/00000542-198608000-00002
Chang CM, Wu TJ, Zhou S, Doshi RN, Lee MH, Ohara T, Fishbein MC, Karagueuzian HS, Chen PS, Chen LS (2001) Nerve sprouting and sympathetic hyperinnervation in a canine model of atrial fibrillation produced by prolonged right atrial pacing. Circulation 103:22–25
Crystal E, Thorpe KE, Connolly SJ, Lamy A, Cybulsky I, Carroll S, Roberts R, Gent M (2004) Metoprolol prophylaxis against postoperative atrial fibrillation increases length of hospital stay in patients not on pre-operative beta blockers: the beta blocker length of stay (BLOS) trial. Heart 90:941–942. doi:10.1136/hrt.2003.016048
Dhingra RC, Deedwania PC, Cummings JM, Amat-Y-Leon F, Wu D, Denes P, Rosen KM (1978) Electrophysiologic effects of lidocaine on sinus node and atrium in patients with and without sinoatrial dysfunction. Circulation 57:448–454
Edwards RH, Rutter WJ, Hanahan D (1989) Directed expression of NGF to pancreatic beta cells in transgenic mice leads to selective hyperinnervation of the islets. Cell 58:161–170. doi:10.1016/0092-8674(89)90412-1
Elvan A, Pride HP, Eble JN, Zipes DP (1995) Radiofrequency catheter ablation of the atria reduces inducibility and duration of atrial fibrillation in dogs. Circulation 91:2235–2244
Freise H, Anthonsen S, Fischer LG, Van Aken HK, Sielenkämper AW (2005) Continuous thoracic epidural anesthesia induces segmental sympathetic block in the awake rat. Anesth Analg 100:255–262. doi:10.1213/01.ANE.0000140253.65577.1C
Gould PA, Yii M, McLean C, Finch S, Marshall T, Lambert GW, Kaye DM (2006) Evidence for increased atrial sympathetic innervation in persistent human atrial fibrillation. Pacing Clin Electrophysiol 29:821–829. doi:10.1111/j.1540-8159.2006.00447.x
Groban L, Zvara DA, Deal DD, Vernon JC, Carpenter RL (1999) Thoracic epidural anesthesia reduces infarct size in a canine model of myocardial ischemia and reperfusion injury. J Cardiothorac Vasc Anesth 13:579–585. doi:10.1016/S1053-0770(99)90011-3
Haghjoo M, Saravi M, Hashemi MJ, Hosseini S, Givtaj N, Ghafarinejad MH, Khamoushi AJ, Emkanjoo Z, Fazelifar AF, Alizadeh A, Sadr-Ameli MA (2007) Optimal beta-blocker for prevention of atrial fibrillation after on-pump coronary artery bypass graft surgery: carvedilol versus metoprolol. Heart Rhythm 4:1170–1174. doi:10.1016/j.hrthm.2007.04.022
Hassankhani A, Steinhelper ME, Soonpaa MH, Katz EB, Taylor DA, Andrade-Rozental A, Factor SM, Steinberg JJ, Field LJ, Federoff HJ (1995) Overexpression of NGF within the heart of transgenic mice causes hyperinnervation, cardiac enlargement, and hyperplasia of ectopic cells. Dev Biol 169:309–321. doi:10.1006/dbio.1995.1146
Heusch G, Baumgart D, Camici P, Chilian W, Gregorini L, Hess O, Indolfi C, Rimoldi O (2000) α-Adrenergic coronary vasoconstriction and myocardial ischemia in humans. Circulation 101:689–694
Heusch G, Deussen A, Thämer V (1985) Cardiac sympathetic nerve activity and progressive vasoconstriction distal to coronary stenoses: feed-back aggravation of myocardial ischemia. J Auton Nerv Syst 13:311–326. doi:10.1016/0165-1838(85)90020-7
Hotvedt R, Platou ES, Refsum H (1983) Electrophysiological effects of thoracic epidural analgesia in the dog heart in situ. Cardiovasc Res 17:259–266. doi:10.1093/cvr/17.5.259
Hopf HB, Weissbach B, Peters J (1990) High thoracic segmental epidural anesthesia diminishes sympathetic outflow to the legs, despite restriction of sensory blockade to the upper thorax. Anesthesiology 73:882–889. doi:10.1097/00000542-199011000-00015
Jayachandran JV, Sih HJ, Winkle W, Zipes DP, Hutchins GD, Olgin JE (2000) Atrial fibrillation produced by prolonged rapid atrial pacing is associated with heterogeneous changes in atrial sympathetic innervation. Circulation 101:1185–1191
Kamibayashi T, Hayashi Y, Mammoto T, Yamatodani A, Taenaka N, Yoshiya I (1995) Thoracic epidural anesthesia attenuates halothane-induced myocardial sensitization to dysrhythmogenic effect of epinephrine in dogs. Anesthesiology 82:129–134. doi:10.1097/00000542-199501000-00017
Kozian A, Schilling T, Hachenberg T (2005) Non-analgetic effects of thoracic epidural anaesthesia. Curr Opin Anaesthesiol 18:29–34. doi:10.1097/00001503-200502000-00006
Li Y, Li WM, Gong YT, Li BX, Liu W, Han W, Dong D, Sheng L, Xue JY, Zhang L, Chu S, Yang BF (2007) The effects of cilazapril and valsartan on the mRNA and protein expressions of atrial calpains and atrial structural remodeling in atrial fibrillation dogs. Basic Res Cardiol 102:245–256. doi:10.1007/s00395-007-0641-8
Liu SS, Block BM, Wu CL (2004) Effects of perioperative central neuraxial analgesia on outcome after coronary artery bypass surgery: a meta-analysis. Anesthesiology 101:153–161. doi:10.1097/00000542-200407000-00024
Mathew JP, Fontes ML, Tudor IC, Ramsay J, Duke P, Mazer CD, Barash PG, Hsu PH, Mangano DT, Investigators of the Ischemia Research and Education Foundation, Multicenter Study of Perioperative Ischemia Research Group (2004) A multicenter risk index for atrial fibrillation after cardiac surgery. JAMA 291:1720–1729. doi:10.1001/jama.291.14.1720
Mayumi T, Dohi S, Takahashi T (1983) Plasma concentrations of lidocaine associated with cervical, thoracic, and lumbar epidural anesthesia. Anesth Analg 62:578–580. doi:10.1213/00000539-198306000-00007
McMurray J, Køber L, Robertson M, Dargie H, Colucci W, Lopez-Sendon J, Remme W, Sharpe DN, Ford I (2005) Antiarrhythmic effect of carvedilol after acute myocardial infarction: results of the Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) trial. J Am Coll Cardiol 45:525–530. doi:10.1016/j.jacc.2004.09.076
Meissner A, Eckardt L, Kirchhof P, Weber T, Rolf N, Breithardt G, Van Aken H, Haverkamp W (2001) Effects of thoracic epidural anesthesia with and without autonomic nervous system blockade on cardiac monophasic action potentials and effective refractoriness in awake dogs. Anesthesiology 95:132–138. doi:10.1097/00000542-200107000-00023
Mihm MJ, Yu F, Carnes CA, Reiser PJ, McCarthy PM, Van Wagoner DR, Bauer JA (2001) Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation. Circulation 104:174–180
Moore CM, Cross MH, Desborough JP, Burrin JM, Macdonald IA, Hall GM (1995) Hormonal effects of thoracic extradural analgesia for cardiac surgery. Br J Anaesth 75:387–393
Oka T, Ozawa Y, Ohkubo Y (2001) Thoracic epidural bupivacaine attenuates supraventricular tachyarrhythmias after pulmonary resection. Anesth Analg 93:253–259. doi:10.1097/00000539-200108000-00003
Olausson K, Magnusdottir H, Lurje L, Wennerblom B, Emanuelsson H, Ricksten SE (1997) Anti-ischemic and anti-anginal effects of thoracic epidural anesthesia versus those of conventional medical therapy in the treatment of severe refractory unstable angina pectoris. Circulation 96:2178–2182
Palomero Rodríguez MA, Suarez Gonzalo L, Villar Alvarez F, Varela Crespo C, Moreno Gomez Limon I, Criado Jimenez A (2008) Thoracic epidural anesthesia decreases C-reactive protein levels in patients undergoing elective coronary artery bypass graft surgery with cardiopulmonary bypass. Minerva Anestesiol 74:619–626
Peters J, Kousoulis L, Arndt JO (1989) Effects of segmental thoracic extradural analgesia on sympathetic block in conscious dogs. Br J Anaesth 63:470–476. doi:10.1093/bja/63.4.470
Pokushalov E, Romanov A, Artyomenko S, Turov A, Shugayev P, Shirokova N, Katritsis DG (2010) Ganglionated plexi ablation for longstanding persistent atrial fibrillation. Europace 12:342–346. doi:10.1093/europace/euq014
Sato R, Koumi S (1995) Modulation of the inwardly rectifying K+ channel in isolated human atrial myocytes by alpha 1-adrenergic stimulation. J Membr Biol 148:185–191. doi:10.1007/BF00207274
Scott NB, Turfrey DJ, Ray DA, Nzewi O, Sutcliffe NP, Lal AB, Norrie J, Nagels WJ, Ramayya GP (2001) A prospective randomized study of the potential benefits of thoracic epidural anesthesia and analgesia in patients undergoing coronary artery bypass grafting. Anesth Analg 93:528–535. doi:10.1097/00000539-200109000-00003
Shakibi JG, Aryanpur I (1979) Electrophysiologic effects of lidocaine in children. Jpn Heart J 20: 271–276
Tan AY, Zhou S, Ogawa M, Song J, Chu M, Li H, Fishbein MC, Lin SF, Chen LS, Chen PS (2008) Neural mechanisms of paroxysmal atrial fibrillation and paroxysmal atrial tachycardia in ambulatory canines. Circulation 118:916–925. doi:10.1161/CIRCULATIONAHA.108.776203
van Veldhuisen DJ, Aass H, El Allaf D, Dunselman PH, Gullestad L, Halinen M, Kjekshus J, Ohlsson L, Wedel H, Wikstrand J, Study Group MERIT-HF (2006) Presence and development of atrial fibrillation in chronic heart failure. Experiences from the MERIT-HF Study. Eur J Heart Fail 8:539–546. doi:10.1016/j.ejheart.2006.01.015
Wernli G, Hasan W, Bhattacherjee A, van Rooijen N, Smith PG (2009) Macrophage depletion suppresses sympathetic hyperinnervation following myocardial infarction. Basic Res Cardiol 104:681–693. doi:10.1007/s00395-009-0033-3
Wichmann J, Ertl G, Höhne W, Schweisfurth H, Wernze H, Kochsiek K (1983) Alpha-receptor restriction of coronary blood flow during atrial fibrillation. Am J Cardiol 52:887–892. doi:10.1016/0002-9149(83)90435-6
Workman AJ (2010) Cardiac adrenergic control and atrial fibrillation. Naunyn-Schmied Arch Pharmacol 381:235–249. doi:10.1007/s00210-009-0474-0
Workman AJ, Kane KA, Russell JA, Norrie J, Rankin AC (2003) Chronic beta-adrenoceptor blockade and human atrial cell electrophysiology: evidence of pharmacological remodelling. Cardiovasc Res 58:518–525. doi:10.1016/S0008-6363(03)00263-3
Zhou S, Cao JM, Tebb ZD, Ohara T, Huang HL, Omichi C, Lee MH, KenKnight BH, Chen LS, Fishbein MC, Karagueuzian HS, Chen P-S (2001) Modulation of QT interval by cardiac sympathetic nerve sprouting and the mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death. J Cardiovasc Electrophysiol 12:1068–1073. doi:10.1046/j.1540-8167.2001.01068.x
Zhou S, Chen LS, Miyauchi Y, Miyauchi M, Kar S, Kangavari S, Fishbein MC, Sharifi B, Chen PS (2004) Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs. Circ Res 95:76–83. doi:10.1161/01.RES.0000133678.22968.e3
Acknowledgments
We would like to thank Mr. Bai-chun Wang for his cardiac surgery support, Ms. Zhen-zi Li for her assistance with the statistical analyses and Feng-qi Liu for his help in HTEA. This study was supported by Harbin Science and Technique Department (No. 2005AA9CS116-1, Wei Han), Heilongjiang Provincial Science and Technique Department (No. QC05C30, Wei Han) and Heilongjiang Provincial Government (LRB05-334, Wei Han).
Conflict of interest
None declared.
Author information
Authors and Affiliations
Corresponding author
Additional information
S. Yang and W. Han contributed equally to this work.
Rights and permissions
About this article
Cite this article
Yang, Ss., Han, W., Cao, Y. et al. Effects of high thoracic epidural anesthesia on atrial electrophysiological characteristics and sympathetic nerve sprouting in a canine model of atrial fibrillation. Basic Res Cardiol 106, 495–506 (2011). https://doi.org/10.1007/s00395-011-0154-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00395-011-0154-3