Advertisement

Vagus nerve stimulation exerts cardioprotection against myocardial ischemia/reperfusion injury predominantly through its efferent vagal fibers

  • Watthana Nuntaphum
  • Wanpitak Pongkan
  • Suwakon Wongjaikam
  • Savitree Thummasorn
  • Pongpan Tanajak
  • Juthamas Khamseekaew
  • Kannaporn Intachai
  • Siriporn C. Chattipakorn
  • Nipon Chattipakorn
  • Krekwit Shinlapawittayatorn
Original Contribution

Abstract

Vagus nerve stimulation (VNS) has been shown to exert cardioprotection against myocardial ischemia/reperfusion (I/R) injury. However, whether the cardioprotection of VNS is mainly due to direct activation through its ipsilateral efferent fibers (motor) rather than indirect effects mediated by the afferent fibers (sensory) have not been clearly understood. We hypothesized that VNS exerts cardioprotection predominantly through its efferent vagal fibers. Thirty swine (30–35 kg) were randomized into five groups: I/R no VNS (I/R), and left mid-cervical VNS with both vagal trunks intact (LC-VNS), with left vagus nerve transection (LtVNX), with right vagus nerve transection (RtVNX) and with atropine pretreatment (Atropine), respectively. VNS was applied at the onset of ischemia (60 min) and continued until the end of reperfusion (120 min). Cardiac function, infarct size, arrhythmia score, myocardial connexin43 expression, apoptotic markers, oxidative stress markers, inflammatory markers (TNF-α and IL-10) and cardiac mitochondrial function, dynamics and fatty acid oxidation (MFN2, OPA1, DRP1, PGC1α and CPT1) were determined. LC-VNS exerted cardioprotection against myocardial I/R injury via improvement of mitochondrial function and dynamics and shifted cardiac fatty acid metabolism toward beta oxidation. However, LC-VNS and LtVNX, both efferent vagal fibers are intact, produced more profound cardioprotection, particularly infarct size reduction, decreased arrhythmia score, oxidative stress and apoptosis and attenuated mitochondrial dysfunction compared to RtVNX. These beneficial effects of VNS were abolished by atropine. Our findings suggest that selective efferent VNS may potentially be effective in attenuating myocardial I/R injury. Moreover, VNS required the contralateral efferent vagal activities to fully provide its cardioprotection.

Keywords

Vagus nerve stimulation Efferent fiber Ischemic/reperfusion injury Cardioprotection 

Notes

Funding

This study was funded by the Thailand Research Fund Royal Golden Jubilee program (STC and NC); a NSTDA Research Chair Grant from the National Science and Technology Development Agency Thailand (NC); the Thailand Research Fund RSA5880015 (KS), RTA6080003 (SCC), and a Chiang Mai University Center of Excellence Award (NC).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest associated with this study.

Ethical approval

All animal procedures were approved by the Faculty of Medicine, Chiang Mai University Institutional Animal Care and Use Committee (Permit No. 33/2554) and investigative procedures were carried out according to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health.

Supplementary material

395_2018_683_MOESM1_ESM.tif (15.4 mb)
Supplementary material 1 (TIFF 15803 kb)
395_2018_683_MOESM2_ESM.tif (22.2 mb)
Supplementary material 2 (TIFF 22740 kb)

References

  1. 1.
    Ahuja P, Zhao P, Angelis E, Ruan H, Korge P, Olson A, Wang Y, Jin ES, Jeffrey FM, Portman M, Maclellan WR (2010) Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice. J Clin Invest 120:1494–1505.  https://doi.org/10.1172/jci38331 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ando M, Katare RG, Kakinuma Y, Zhang D, Yamasaki F, Muramoto K, Sato T (2005) Efferent vagal nerve stimulation protects heart against ischemia-induced arrhythmias by preserving connexin43 protein. Circulation 112:164–170.  https://doi.org/10.1161/circulationaha.104.525493 CrossRefPubMedGoogle Scholar
  3. 3.
    Atherton PJ, Babraj J, Smith K, Singh J, Rennie MJ, Wackerhage H (2005) Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. Faseb J 19:786–788.  https://doi.org/10.1096/fj.04-2179fje CrossRefPubMedGoogle Scholar
  4. 4.
    Basalay MV, Mastitskaya S, Mrochek A, Ackland GL, del Arroyo AG, Sanchez J, Sjoquist P-O, Pernow J, Gourine AV, Gourine A (2016) Glucagon-like peptide-1 (GLP-1) mediates cardioprotection by remote ischaemic conditioning. Cardiovasc Res 112:669–676.  https://doi.org/10.1093/cvr/cvw216 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bhatt MP, Lim Y-C, Kim Y-M, Ha K-S (2013) C-peptide activates AMPKα and prevents ROS-mediated mitochondrial fission and endothelial apoptosis in diabetes. Diabetes 62:3851–3862.  https://doi.org/10.2337/db13-0039 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Boengler K, Ruiz-Meana M, Gent S, Ungefug E, Soetkamp D, Miro-Casas E, Cabestrero A, Fernandez-Sanz C, Semenzato M, Di Lisa F, Rohrbach S, Garcia-Dorado D, Heusch G, Schulz R (2012) Mitochondrial connexin 43 impacts on respiratory complex I activity and mitochondrial oxygen consumption. J Cell Mol Med 16:1649–1655.  https://doi.org/10.1111/j.1582-4934.2011.01516.x CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Brack KE, Winter J, Ng GA (2013) Mechanisms underlying the autonomic modulation of ventricular fibrillation initiation—tentative prophylactic properties of vagus nerve stimulation on malignant arrhythmias in heart failure. Heart Fail Rev 18:389–408.  https://doi.org/10.1007/s10741-012-9314-2 CrossRefPubMedGoogle Scholar
  8. 8.
    Brown DA, Aon MA, Akar FG, Liu T, Sorarrain N, O’Rourke B (2008) Effects of 4′-chlorodiazepam on cellular excitation-contraction coupling and ischaemia-reperfusion injury in rabbit heart. Cardiovasc Res 79:141–149.  https://doi.org/10.1093/cvr/cvn053 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Brown DA, O’Rourke B (2010) Cardiac mitochondria and arrhythmias. Cardiovasc Res 88:241–249.  https://doi.org/10.1093/cvr/cvq231 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Calvillo L, Vanoli E, Andreoli E, Besana A, Omodeo E, Gnecchi M, Zerbi P, Vago G, Busca G, Schwartz PJ (2011) Vagal stimulation, through its nicotinic action, limits infarct size and the inflammatory response to myocardial ischemia and reperfusion. J Cardiovasc Pharmacol 58:500–507.  https://doi.org/10.1097/FJC.0b013e31822b7204 CrossRefPubMedGoogle Scholar
  11. 11.
    Chan DC (2012) Fusion and fission: interlinked processes critical for mitochondrial health. Annu Rev Genet 46:265–287.  https://doi.org/10.1146/annurev-genet-110410-132529 CrossRefPubMedGoogle Scholar
  12. 12.
    Chang CR, Blackstone C (2010) Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1. Ann N Y Acad Sci 1201:34–39.  https://doi.org/10.1111/j.1749-6632.2010.05629.x CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Chen H, Chan DC (2010) Physiological functions of mitochondrial fusion. Ann N Y Acad Sci 1201:21–25.  https://doi.org/10.1111/j.1749-6632.2010.05615.x CrossRefPubMedGoogle Scholar
  14. 14.
    Chinda K, Palee S, Surinkaew S, Phornphutkul M, Chattipakorn S, Chattipakorn N (2013) Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury. Int J Cardiol 167:451–457.  https://doi.org/10.1016/j.ijcard.2012.01.011 CrossRefPubMedGoogle Scholar
  15. 15.
    Chunchai T, Samniang B, Sripetchwandee J, Pintana H, Pongkan W, Kumfu S, Shinlapawittayatorn K, KenKnight BH, Chattipakorn N, Chattipakorn SC (2016) Vagus nerve stimulation exerts the neuroprotective effects in obese-insulin resistant rats, leading to the improvement of cognitive function. Sci Rep 6:26866.  https://doi.org/10.1038/srep26866 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Coote JH (2013) Myths and realities of the cardiac vagus. J Physiol 591:4073–4085.  https://doi.org/10.1113/jphysiol.2013.257758 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Curtis MJ, Hancox JC, Farkas A, Wainwright CL, Stables CL, Saint DA, Clements-Jewery H, Lambiase PD, Billman GE, Janse MJ, Pugsley MK, Ng GA, Roden DM, Camm AJ, Walker MJ (2013) The Lambeth Conventions (II): guidelines for the study of animal and human ventricular and supraventricular arrhythmias. Pharmacol Ther 139:213–248.  https://doi.org/10.1016/j.pharmthera.2013.04.008 CrossRefPubMedGoogle Scholar
  18. 18.
    D’Souza A, Bucchi A, Johnsen AB, Logantha SJ, Monfredi O, Yanni J, Prehar S, Hart G, Cartwright E, Wisloff U, Dobryznski H, DiFrancesco D, Morris GM, Boyett MR (2014) Exercise training reduces resting heart rate via downregulation of the funny channel HCN4. Nat Commun 5:3775.  https://doi.org/10.1038/ncomms4775 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Danson EJF, Paterson DJ (2003) Enhanced neuronal nitric oxide synthase expression is central to cardiac vagal phenotype in exercise-trained mice. J Physiol 546:225–232.  https://doi.org/10.1113/jphysiol.2002.031781 CrossRefPubMedGoogle Scholar
  20. 20.
    De Ferrari GM, Crijns HJ, Borggrefe M, Milasinovic G, Smid J, Zabel M, Gavazzi A, Sanzo A, Dennert R, Kuschyk J, Raspopovic S, Klein H, Swedberg K, Schwartz PJ (2011) Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. Eur Heart J 32:847–855.  https://doi.org/10.1093/eurheartj/ehq391 CrossRefPubMedGoogle Scholar
  21. 21.
    Di Lisa F, Bernardi P (2006) Mitochondria and ischemia-reperfusion injury of the heart: fixing a hole. Cardiovasc Res 70:191–199.  https://doi.org/10.1016/j.cardiores.2006.01.016 CrossRefPubMedGoogle Scholar
  22. 22.
    Dicarlo L, Libbus I, Amurthur B, Kenknight BH, Anand IS (2013) Autonomic regulation therapy for the improvement of left ventricular function and heart failure symptoms: the ANTHEM-HF study. J Card Fail 19:655–660.  https://doi.org/10.1016/j.cardfail.2013.07.002 CrossRefPubMedGoogle Scholar
  23. 23.
    Donato M, Buchholz B, Rodriguez M, Perez V, Inserte J, Garcia-Dorado D, Gelpi RJ (2013) Role of the parasympathetic nervous system in cardioprotection by remote hindlimb ischaemic preconditioning. Exp Physiol 98:425–434.  https://doi.org/10.1113/expphysiol.2012.066217 CrossRefPubMedGoogle Scholar
  24. 24.
    Dvorakova M, Lips KS, Bruggmann D, Slavikova J, Kuncova J, Kummer W (2005) Developmental changes in the expression of nicotinic acetylcholine receptor alpha-subunits in the rat heart. Cell Tissue Res 319:201–209.  https://doi.org/10.1007/s00441-004-1008-1 CrossRefPubMedGoogle Scholar
  25. 25.
    Hauptman PJ, Schwartz PJ, Gold MR, Borggrefe M, Van Veldhuisen DJ, Starling RC, Mann DL (2012) Rationale and study design of the increase of vagal tone in heart failure study: INOVATE-HF. Am Heart J 163(954–962):e951.  https://doi.org/10.1016/j.ahj.2012.03.021 CrossRefGoogle Scholar
  26. 26.
    Heusch G (2015) Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res 116:674–699.  https://doi.org/10.1161/circresaha.116.305348 CrossRefPubMedGoogle Scholar
  27. 27.
    Heusch G (2017) Vagal cardioprotection in reperfused acute myocardial infarction. JACC Cardiovasc Interv 10:1521–1522.  https://doi.org/10.1016/j.jcin.2017.05.063 CrossRefPubMedGoogle Scholar
  28. 28.
    Heusch G, Deussen A, Thamer 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.  https://doi.org/10.1016/0165-1838(85)90020-7 CrossRefPubMedGoogle Scholar
  29. 29.
    Katare RG, Ando M, Kakinuma Y, Arikawa M, Handa T, Yamasaki F, Sato T (2009) Vagal nerve stimulation prevents reperfusion injury through inhibition of opening of mitochondrial permeability transition pore independent of the bradycardiac effect. J Thorac Cardiovasc Surg 137:223–231.  https://doi.org/10.1016/j.jtcvs.2008.08.020 CrossRefPubMedGoogle Scholar
  30. 30.
    Kleinbongard P, Skyschally A, Heusch G (2017) Cardioprotection by remote ischemic conditioning and its signal transduction. Pflugers Arch 469:159–181.  https://doi.org/10.1007/s00424-016-1922-6 CrossRefPubMedGoogle Scholar
  31. 31.
    Kong SS, Liu JJ, Yu XJ, Lu Y, Zang WJ (2012) Protection against ischemia-induced oxidative stress conferred by vagal stimulation in the rat heart: involvement of the AMPK-PKC pathway. Int J Mol Sci 13:14311–14325.  https://doi.org/10.3390/ijms131114311 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Li DL, Liu BH, Sun L, Zhao M, He X, Yu XJ, Zang WJ (2010) Alterations of muscarinic acetylcholine receptors-2, 4 and alpha7-nicotinic acetylcholine receptor expression after ischaemia/reperfusion in the rat isolated heart. Clin Exp Pharmacol Physiol 37:1114–1119.  https://doi.org/10.1111/j.1440-1681.2010.05448.x CrossRefPubMedGoogle Scholar
  33. 33.
    Li F, Fan X, Zhang Y, Pang L, Ma X, Song M, Kou J, Yu B (2016) Cardioprotection by combination of three compounds from ShengMai preparations in mice with myocardial ischemia/reperfusion injury through AMPK activation-mediated mitochondrial fission. Sci Rep 6:37114.  https://doi.org/10.1038/srep37114 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Libbus I, Nearing BD, Amurthur B, KenKnight BH, Verrier RL (2016) Autonomic regulation therapy suppresses quantitative T-wave alternans and improves baroreflex sensitivity in patients with heart failure enrolled in the ANTHEM-HF study. Heart Rhythm 13:721–728.  https://doi.org/10.1016/j.hrthm.2015.11.030 CrossRefPubMedGoogle Scholar
  35. 35.
    Liu J, Wang H, Li J (2016) Inflammation and inflammatory cells in myocardial infarction and reperfusion injury: a double-edged sword. Clin Med Insights Cardiol 10:79–84.  https://doi.org/10.4137/CMC.S33164 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Mastitskaya S, Marina N, Gourine A, Gilbey MP, Spyer KM, Teschemacher AG, Kasparov S, Trapp S, Ackland GL, Gourine AV (2012) Cardioprotection evoked by remote ischaemic preconditioning is critically dependent on the activity of vagal pre-ganglionic neurones. Cardiovasc Res 95:487–494.  https://doi.org/10.1093/cvr/cvs212 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Mateos R, Lecumberri E, Ramos S, Goya L, Bravo L (2005) Determination of malondialdehyde (MDA) by high-performance liquid chromatography in serum and liver as a biomarker for oxidative stress. Application to a rat model for hypercholesterolemia and evaluation of the effect of diets rich in phenolic antioxidants from fruits. J Chromatogr B Analyt Technol Biomed Life Sci 827:76–82.  https://doi.org/10.1016/j.jchromb.2005.06.035 CrossRefPubMedGoogle Scholar
  38. 38.
    Mavropoulos SA, Khan NS, Levy ACJ, Faliks BT, Sison CP, Pavlov VA, Zhang Y, Ojamaa K (2017) Nicotinic acetylcholine receptor-mediated protection of the rat heart exposed to ischemia reperfusion. Mol Med.  https://doi.org/10.2119/molmed.2017.00091 PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Miller TD, Christian TF, Hopfenspirger MR, Hodge DO, Gersh BJ, Gibbons RJ (1995) Infarct size after acute myocardial infarction measured by quantitative tomographic 99mTc sestamibi imaging predicts subsequent mortality. Circulation 92:334–341.  https://doi.org/10.1161/01.CIR.92.3.334 CrossRefPubMedGoogle Scholar
  40. 40.
    Palee S, Weerateerangkul P, Chinda K, Chattipakorn SC, Chattipakorn N (2013) Mechanisms responsible for beneficial and adverse effects of rosiglitazone in a rat model of acute cardiac ischaemia-reperfusion. Exp Physiol 98:1028–1037.  https://doi.org/10.1113/expphysiol.2012.070433 CrossRefPubMedGoogle Scholar
  41. 41.
    Patel YA, Saxena T, Bellamkonda RV, Butera RJ (2017) Kilohertz frequency nerve block enhances anti-inflammatory effects of vagus nerve stimulation. Sci Rep 7:39810.  https://doi.org/10.1038/srep39810 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Premchand RK, Sharma K, Mittal S, Monteiro R, Dixit S, Libbus I, DiCarlo LA, Ardell JL, Rector TS, Amurthur B, KenKnight BH, Anand IS (2014) Autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure: results of the ANTHEM-HF trial. J Card Fail 20:808–816.  https://doi.org/10.1016/j.cardfail.2014.08.009 CrossRefPubMedGoogle Scholar
  43. 43.
    Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24:981–990.  https://doi.org/10.1016/j.cellsig.2012.01.008 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Samniang B, Shinlapawittayatorn K, Chunchai T, Pongkan W, Kumfu S, Chattipakorn SC, KenKnight BH, Chattipakorn N (2016) Vagus nerve stimulation improves cardiac function by preventing mitochondrial dysfunction in obese-insulin resistant rats. Sci Rep 6:19749.  https://doi.org/10.1038/srep19749 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Schwartz PJ, De Ferrari GM, Sanzo A, Landolina M, Rordorf R, Raineri C, Campana C, Revera M, Ajmone-Marsan N, Tavazzi L, Odero A (2008) Long term vagal stimulation in patients with advanced heart failure: first experience in man. Eur J Heart Fail 10:884–891.  https://doi.org/10.1016/j.ejheart.2008.07.016 CrossRefPubMedGoogle Scholar
  46. 46.
    Shinlapawittayatorn K, Chinda K, Palee S, Surinkaew S, Kumfu S, Kumphune S, Chattipakorn S, KenKnight BH, Chattipakorn N (2014) Vagus nerve stimulation initiated late during ischemia, but not reperfusion, exerts cardioprotection via amelioration of cardiac mitochondrial dysfunction. Heart Rhythm 11:2278–2287.  https://doi.org/10.1016/j.hrthm.2014.08.001 CrossRefPubMedGoogle Scholar
  47. 47.
    Shinlapawittayatorn K, Chinda K, Palee S, Surinkaew S, Thunsiri K, Weerateerangkul P, Chattipakorn S, KenKnight BH, Chattipakorn N (2013) Low-amplitude, left vagus nerve stimulation significantly attenuates ventricular dysfunction and infarct size through prevention of mitochondrial dysfunction during acute ischemia-reperfusion injury. Heart Rhythm 10:1700–1707.  https://doi.org/10.1016/j.hrthm.2013.08.009 CrossRefPubMedGoogle Scholar
  48. 48.
    Sun L, Zhao M, Yu XJ, Wang H, He X, Liu JK, Zang WJ (2013) Cardioprotection by acetylcholine: a novel mechanism via mitochondrial biogenesis and function involving the PGC-1alpha pathway. J Cell Physiol 228:1238–1248.  https://doi.org/10.1002/jcp.24277 CrossRefPubMedGoogle Scholar
  49. 49.
    Terada S, Goto M, Kato M, Kawanaka K, Shimokawa T, Tabata I (2002) Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle. Biochem Biophys Res Commun 296:350–354.  https://doi.org/10.1016/S0006-291X(02)00881-1 CrossRefPubMedGoogle Scholar
  50. 50.
    Thummasorn S, Kumfu S, Chattipakorn S, Chattipakorn N (2011) Granulocyte-colony stimulating factor attenuates mitochondrial dysfunction induced by oxidative stress in cardiac mitochondria. Mitochondrion 11:457–466.  https://doi.org/10.1016/j.mito.2011.01.008 CrossRefPubMedGoogle Scholar
  51. 51.
    Uitterdijk A, Yetgin T, te Lintel Hekkert M, Sneep S, Krabbendam-Peters I, van Beusekom HM, Fischer TM, Cornelussen RN, Manintveld OC, Merkus D, Duncker DJ (2015) Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow. Basic Res Cardiol 110:508.  https://doi.org/10.1007/s00395-015-0508-3 CrossRefPubMedGoogle Scholar
  52. 52.
    Wang Q, Liu GP, Xue FS, Wang SY, Cui XL, Li RP, Yang GZ, Sun C, Liao X (2015) Combined vagal stimulation and limb remote ischemic perconditioning enhances cardioprotection via an anti-inflammatory pathway. Inflammation 38:1748–1760.  https://doi.org/10.1007/s10753-015-0152-y CrossRefPubMedGoogle Scholar
  53. 53.
    Whelan RS, Kaplinskiy V, Kitsis RN (2010) Cell death in the pathogenesis of heart disease: mechanisms and significance. Annu Rev Physiol 72:19–44.  https://doi.org/10.1146/annurev.physiol.010908.163111 CrossRefPubMedGoogle Scholar
  54. 54.
    Wu W, Lu Z (2011) Loss of anti-arrhythmic effect of vagal nerve stimulation on ischemia-induced ventricular tachyarrhythmia in aged rats. Tohoku J Exp Med 223:27–33.  https://doi.org/10.1620/tjem.223.27 CrossRefPubMedGoogle Scholar
  55. 55.
    Xue RQ, Sun L, Yu XJ, Li DL, Zang WJ (2017) Vagal nerve stimulation improves mitochondrial dynamics via an M3 receptor/CaMKKbeta/AMPK pathway in isoproterenol-induced myocardial ischaemia. J Cell Mol Med 21:58–71.  https://doi.org/10.1111/jcmm.12938 CrossRefPubMedGoogle Scholar
  56. 56.
    Yamakawa K, Rajendran PS, Takamiya T, Yagishita D, So EL, Mahajan A, Shivkumar K, Vaseghi M (2015) Vagal nerve stimulation activates vagal afferent fibers that reduce cardiac efferent parasympathetic effects. Am J Physiol Heart Circ Physiol 309:H1579–H1590.  https://doi.org/10.1152/ajpheart.00558.2015 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Yan W, Zhang H, Liu P, Wang H, Liu J, Gao C, Liu Y, Lian K, Yang L, Sun L, Guo Y, Zhang L, Dong L, Lau WB, Gao E, Gao F, Xiong L, Wang H, Qu Y, Tao L (2013) Impaired mitochondrial biogenesis due to dysfunctional adiponectin-AMPK-PGC-1alpha signaling contributing to increased vulnerability in diabetic heart. Basic Res Cardiol 108:329.  https://doi.org/10.1007/s00395-013-0329-1 CrossRefPubMedGoogle Scholar
  58. 58.
    Yarana C, Sripetchwandee J, Sanit J, Chattipakorn S, Chattipakorn N (2012) Calcium-induced cardiac mitochondrial dysfunction is predominantly mediated by cyclosporine A-dependent mitochondrial permeability transition pore. Arch Med Res 43:333–338.  https://doi.org/10.1016/j.arcmed.2012.06.010 CrossRefPubMedGoogle Scholar
  59. 59.
    Yellon DM, Hausenloy DJ (2007) Myocardial reperfusion injury. N Engl J Med 357:1121–1135.  https://doi.org/10.1056/NEJMra071667 CrossRefPubMedGoogle Scholar
  60. 60.
    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
  61. 61.
    Yuan H, Silberstein SD (2016) Vagus nerve and vagus nerve stimulation, a comprehensive review: part I. Headache 56:71–78.  https://doi.org/10.1111/head.12647 CrossRefPubMedGoogle Scholar
  62. 62.
    Zannad F, De Ferrari GM, Tuinenburg AE, Wright D, Brugada J, Butter C, Klein H, Stolen C, Meyer S, Stein KM, Ramuzat A, Schubert B, Daum D, Neuzil P, Botman C, Castel MA, D’Onofrio A, Solomon SD, Wold N, Ruble SB (2015) Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial. Eur Heart J 36:425–433.  https://doi.org/10.1093/eurheartj/ehu345 CrossRefPubMedGoogle Scholar
  63. 63.
    Zhao M, He X, Bi XY, Yu XJ, Gil Wier W, Zang WJ (2013) Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion. Basic Res Cardiol 108:345.  https://doi.org/10.1007/s00395-013-0345-1 CrossRefPubMedGoogle Scholar
  64. 64.
    Zhao M, Sun L, Yu XJ, Miao Y, Liu JJ, Wang H, Ren J, Zang WJ (2013) Acetylcholine mediates AMPK-dependent autophagic cytoprotection in H9c2 cells during hypoxia/reoxygenation injury. Cell Physiol Biochem 32:601–613.  https://doi.org/10.1159/000354464 CrossRefPubMedGoogle Scholar
  65. 65.
    Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI (2002) AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci USA 99:15983–15987.  https://doi.org/10.1073/pnas.252625599 CrossRefPubMedGoogle Scholar
  66. 66.
    Zorzano A, Liesa M, Sebastian D, Segales J, Palacin M (2010) Mitochondrial fusion proteins: dual regulators of morphology and metabolism. Semin Cell Dev Biol 21:566–574.  https://doi.org/10.1016/j.semcdb.2010.01.002 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Watthana Nuntaphum
    • 1
    • 2
    • 3
  • Wanpitak Pongkan
    • 1
    • 2
    • 3
  • Suwakon Wongjaikam
    • 1
    • 2
    • 3
  • Savitree Thummasorn
    • 1
    • 2
    • 3
  • Pongpan Tanajak
    • 1
    • 2
    • 3
  • Juthamas Khamseekaew
    • 1
    • 2
    • 3
  • Kannaporn Intachai
    • 1
    • 2
    • 3
  • Siriporn C. Chattipakorn
    • 1
    • 2
    • 3
    • 4
  • Nipon Chattipakorn
    • 1
    • 2
    • 3
  • Krekwit Shinlapawittayatorn
    • 1
    • 2
    • 3
  1. 1.Faculty of Medicine, Cardiac Electrophysiology Research and Training CenterChiang Mai UniversityChiang MaiThailand
  2. 2.Cardiac Electrophysiology Unit, Department of Physiology, Faculty of MedicineChiang Mai UniversityChiang MaiThailand
  3. 3.Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai UniversityChiang MaiThailand
  4. 4.Department of Oral Biology and Diagnostic Sciences, Faculty of DentistryChiang Mai UniversityChiang MaiThailand

Personalised recommendations