Closed-loop control of the heart rate by electrical stimulation of the vagus nerve

  • Marco Tosato
  • Ken Yoshida
  • Egon Toft
  • Vitas Nekrasas
  • Johannes J. Struijk


Stimulation of the vagus nerve potentially decreases the risk of sudden cardiac death. An improvement of the technique would be its regulation using the heart rate (HR) as a feedback variable. We address the possibility of closed-loop control of the HR, focusing on the stimulation parameters, nerve fibre populations and the reproducibility of the cardiovascular response. The response to electrical stimulation of the vagus nerve was studied in seven acute experiments on pigs. Feedback regulation of the HR over periods of 5 min was carried out. Three main populations of myelinated fibres were found. The performance of the controller was significantly better at amplitudes higher than those needed for stimulation of the myelinated components only. A 18% change in the duration of the RR interval could be controlled in all experiments. The possibility of closed-loop control of the HR seems to be promising.


Vagus nerve Vagal compound action potential Electrical stimulation Heart rate Closed-loop control 



The authors thank Dr Henrik Barlebo for access to the Biolab and helping to make this study possible. We also thank Ole Sørensen, Torben Madsen and Jens Sørensen, for their useful technical suggestions and help in handling the animals. This work was supported by the European Commission for the NeuralPRO Network (FP5-Program, Research and Training Network).


  1. 1.
    Agostoni E, Chinnock JE, Daly MDB, Murray JG (1957) Functional and histological studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera in the cat. J Physiol (Lond) 135:182–205Google Scholar
  2. 2.
    Ali II, Pirzada NA, Kanjwal Y, Wannamaker B, Medhkour A, Koltz MT, Vaughn BV (2004) Complete heart block with ventricular asystole during left vagus nerve stimulation for epilepsy. Epilepsy Behav 5:768–771CrossRefPubMedGoogle Scholar
  3. 3.
    Ben Menachem E (2002) Vagus-nerve stimulation for the treatment of epilepsy. Lancet Neurol 1:477–482CrossRefPubMedGoogle Scholar
  4. 4.
    Bilgutay AM, Bilgutay IM, Merkel FK, Lillehei CW (1968) Vagal tuning—a new concept in treatment of supraventricular arrhythmias angina pectoris and heart failure. J Thoracic Cardiovasc Surg 56:71–82Google Scholar
  5. 5.
    Billman GE, Hoskins RS, Randall DC, Randall WC, Hamlin RL, Lin YC (1989) Selective vagal postganglionic innervation of the sinoatrial and atrioventricular nodes in the non-human primate. J Auton Nerv Syst 26:27–36CrossRefPubMedGoogle Scholar
  6. 6.
    Bishop O (2000) Understand electronic control systems. Newnes, Oxford, UKGoogle Scholar
  7. 7.
    Buckley NM, Gootman PM, Brazeau P, Matanic BP, Frasier ID, Gentles EL (1979) Cardiovascular function in anesthetized miniature swine. Lab Anim Sci 29(2):200–208PubMedGoogle Scholar
  8. 8.
    Cheng ZX, Powley TL (2000) Nucleus ambiguus projections to cardiac ganglia of rat atria: An anterograde tracing study. J Comp Neurol 424:588–606CrossRefPubMedGoogle Scholar
  9. 9.
    Cohn AE, Lewis T (1913) The predominant influence of the left vagus nerve upon conduction between the auricles and ventricles in the dog. J Exp Med 18:739–747CrossRefGoogle Scholar
  10. 10.
    Dexter F, Levy MN, Rudy Y (1989) Mathematical-model of the changes in heart-rate elicited by vagal-stimulation. Circ Res 65:1330–1339PubMedGoogle Scholar
  11. 11.
    Erlanger J, Gasser HS (1937) Electrical signs of nervous activity. University of Pennsylvania Press, Philadelphia, PAGoogle Scholar
  12. 12.
    Evans MS, Verma-Ahuja S, Naritoku DK, Espinosa JA (2004) Intraoperative human vagus nerve compound action potentials. Acta Neurol Scand 110:232–238CrossRefPubMedGoogle Scholar
  13. 13.
    Ford TW, Mcwilliam PN (1986) The effects of electrical-stimulation of myelinated and nonmyelinated vagal fibers on heart-rate in the rabbit. J Physiol (Lond) 380:341–347Google Scholar
  14. 14.
    Frei MG, Osorio I (2001) Left vagus nerve stimulation with the neurocybernetic prosthesis has complex effects on heart rate and on its variability in humans. Epilepsia 42:1007–1016CrossRefPubMedGoogle Scholar
  15. 15.
    Furlan R, Diedrich A, Rimoldi A, Palazzolo L, Porta C, Diedrich L, Harris PA, Sleight P, Biagioni I, Robertson D, Bernardi L (2003) Effects of unilateral and bilateral carotid baroreflex stimulation on cardiac and neural sympathetic discharge oscillatory patterns. Circulation 108(6):717–23CrossRefPubMedGoogle Scholar
  16. 16.
    Haugland M. (1996) A flexible method for fabrication of nerve cuff electrodes. In: Proceedings of the 18th annual international conference of the IEEE, Bridging disciplines for biomedicine. Eng Med Biol Soc 1:359–360Google Scholar
  17. 17.
    Jones JFX, Wang Y, Jordan D (1995) Heart-rate responses to selective stimulation of cardiac vagal-C fibers in anesthetized cats, rats and rabbits. J Physiol (Lond) 489:203–214Google Scholar
  18. 18.
    Jones JFX, Wang Y, Jordan D (1998) Activity of C fibre cardiac vagal efferents in anaesthetized cats and rats. J Physiol (Lond) 507:869–880CrossRefGoogle Scholar
  19. 19.
    Kawada T, Ikeda Y, Sugimachi M, Shishido T, Kawaguchi O, Yamazaki T, Alexander J, Sunagawa K (1996) Bidirectional augmentation of heart rate regulation by autonomic nervous system in rabbits. Am J Physiol Heart Circ Physiol 40:H288–H295Google Scholar
  20. 20.
    Koo B, Ham SD, Sood S, Tarver B (2001) Human vagus nerve electrophysiology—a guide to vagus nerve stimulation parameters. J Clin Neurophysiol 18:429–433CrossRefPubMedGoogle Scholar
  21. 21.
    Kunze DL (1972) Reflex discharge patterns of cardiac vagal efferent fibers. J Physiol (Lond) 222:1–15Google Scholar
  22. 22.
    Kuo BC (1991) Automatic control systems. Prentice Hall, Englewood Cliffs, NJGoogle Scholar
  23. 23.
    Li M, Zheng C, Sato T, Kawada T, Sugimachi M, Sunagawa K (2004) Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats. Circulation 109:120–124CrossRefPubMedGoogle Scholar
  24. 24.
    Mancia G, Ferrari A, Gregorini L, Valentini R, Ludbrook J, Zanchetti A (1977) Circulatory reflexes from carotid and extracarotid baroreceptor areas in man. Circ Results 41(3):309–15Google Scholar
  25. 25.
    Matheny RG, Shaar CJ (1997) Vagus nerve stimulation as a method to temporarily slow or arrest the heart. Ann Thorac Surg 63:S28–S29CrossRefPubMedGoogle Scholar
  26. 26.
    Middleton S, Middleton HH, Grundfest H (1950) Spike potentials and cardiac effects of mammalian vagus nerve. Am J Physiol 162:545–552PubMedGoogle Scholar
  27. 27.
    Parker P, Celler BG, Potter EK, Mccloskey DI (1984) Vagal-stimulation and cardiac slowing. J Auton Nerv Syst 11:226–231CrossRefPubMedGoogle Scholar
  28. 28.
    Piterman L, Zimmet H, Krum H, Tonkin A, Yallop J (2005) Chronic heart failure—optimising care in general practice. Aust Fam Physician 34(7):547–553PubMedGoogle Scholar
  29. 29.
    Prakash P, Safanie AH (1967) Asymmetrical distribution of aortic nerve fibers in pig. Anat Rec 158:51–57CrossRefPubMedGoogle Scholar
  30. 30.
    Randall WC, Milosavljevic M, Wurster RD, Geis GS, Ardell JL (1986) Selective vagal innervation of the heart. Ann Clin Lab Sci 16:198–208PubMedGoogle Scholar
  31. 31.
    Routledge HC, Chowdhary S, Townend JN (2002) Heart rate variability—a therapeutic target? J Clin Pharm Ther 27(2):85–92CrossRefPubMedGoogle Scholar
  32. 32.
    Sloan TB (1998) Anesthetic effects on electrophysiologic recordings. J Clin Neurophysiol 15(3):217–226CrossRefPubMedGoogle Scholar
  33. 33.
    Swindle MM (1998) Surgery, anaesthesia, and experimental techniques in Swine. Iowa State University Press, Ames, IAGoogle Scholar
  34. 34.
    Tosato M, Yoshida K, Toft E, Struijk JJ (2005) Characterization of the cardiac response to vagal nerve stimulation. In: 2nd international IEEE EMBS conference on March 16–19, Neural Eng 1:540–542Google Scholar
  35. 35.
    Vanoli E, Deferrari GM, Strambabadiale M, Hull SS, Foreman RD, Schwartz PJ (1991) Vagal-stimulation and prevention of sudden-death in conscious dogs with a healed myocardial-infarction. Circ Res 68:1471–1481PubMedGoogle Scholar
  36. 36.
    Waninger MS, Bourland JD, Geddes LA, Schoenlein WE, Graber G, Weirich WE, Wodicka GR (2000) Electrophysiological control of ventricular rate during atrial fibrillation. Pace-Pacing Clin Electrophysiol 23:1239–1244PubMedGoogle Scholar
  37. 37.
    Warner HR, Cox A (1962) A mathematical model of heart rate control by sympathetic and vagus efferent information. J Appl Physiol 17:349–355PubMedGoogle Scholar
  38. 38.
    Zhang YH, Mowrey KA, Zhuang SW, Wallick DW, Popovic ZB, Mazgalev TN (2002) Optimal ventricular rate slowing during atrial fibrillation by feedback AV nodal-selective vagal stimulation. Am J Physiol Heart Circ Physiol 282:H1102–H1110PubMedGoogle Scholar

Copyright information

© International Federation for Medical and Biological Engineering 2006

Authors and Affiliations

  • Marco Tosato
    • 1
  • Ken Yoshida
    • 1
  • Egon Toft
    • 1
    • 2
  • Vitas Nekrasas
    • 3
  • Johannes J. Struijk
    • 1
  1. 1.Center for Sensory-Motor Interaction (SMI), Department of Health Science and TechnologyAalborg UniversityAalborg EastDenmark
  2. 2.Department of Cardiology, Aalborg Hospital Aarhus University HospitalAalborgDenmark
  3. 3.Department of Thoracic Surgery, Aalborg HospitalAarhus University HospitalAalborgDenmark

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