How to Induce Arrhythmias with Adenosine?

  • Simona Căinap


Adenosine is a nucleoside that is normally found inside the human body. It has a negative chronotropic and dromotropic effect. It slows the sinus node rate and also the conduction through the AV node. Adenosine’s mechanism of action is mainly on the sinus node and atrioventricular node. It stimulates the potassium current Ikr, Ado and Ach , inducing cellular hyperpolarization and blocking the conduction through the AV node with subsequent interruption of PSVT that is node-dependent. Adenosine can induce reentry using an accessory pathway. By slowing the anterograde conduction through the AV node, it allows retrograde activation of the atrium through the accessory pathway. Human studies have also demonstrated that adenosine administration reveals dormant PV conduction. The ADVICE trial demonstrated that 53% of the patients that received adenosine had dormant conduction.


  1. 1.
    Honey R, Ritchie W, Thomson W. The action of adenosine upon the human heart. Q J Med. 1930;23:485–9.CrossRefGoogle Scholar
  2. 2.
    Lerman BB, Belardinelli L. Cardiac electrophysiology of adenosine. Basic and clinical concepts. Circulation. 1991;83:1499–509.CrossRefGoogle Scholar
  3. 3.
    Jaeggi E, Chiu C, Hamilton R, Gilljam T, Gow R. Adenosine induced atrial pro-arrhythmia in children. Can J Cardiol. 1999;15:169–72.PubMedGoogle Scholar
  4. 4.
    Moro C, Lorio N, Nuñez A, Martinez J, Novo L, Aguilera M, et al. Dose related efficacy of adenosine triphosphate in spontaneous supraventricular tachyarrhythmias. Int J Cardiol. 1989;25:207–12.CrossRefGoogle Scholar
  5. 5.
    Liu J, Huang CX, Jiang H, Bao MW, Cao F, Wang T. Characteristics of hyperpolarization-activated inward current in rabbit pulmonary vein muscle sleeve cells. Chin Med J. 2005;118:2014–9.PubMedGoogle Scholar
  6. 6.
    Ukena D, Schudt C, Sybrecht GW. Adenosine receptor blocking xanthines as inhibitors of phosphodiesterase isozymes. Biochem Pharmacol. 1993;45:847–51.CrossRefGoogle Scholar
  7. 7.
    Hashimoto T, Young WL, Aagaard BD, Joshi S, Ostapkovich ND, Pile-Spellman J. Adenosine-induced ventricular asystole to induce transient profound systemic hypotension in patients undergoing endovascular therapy. Dose-response characteristics. Anesthesiology. 2000;93:998–1001.CrossRefGoogle Scholar
  8. 8.
    Gil Madre J, Lázaro Rodriguez S, Sentenac Merchan G, Sepulveda Berocal MA, Alises Moraleda JM, Cortes Bermejo S, et al. Adenosine triphosphate in the treatment of supraventricular paroxysmal tachycardia: a comparison with verapamil. Rev Esp Cardiol. 1995;48:55–8.PubMedGoogle Scholar
  9. 9.
    Drury AN, Szent-Gyorgyi A. The physiological activity of adenine compounds with special reference to their action upon the mammalian heart. J Physiol. 1929;68:213–37.CrossRefGoogle Scholar
  10. 10.
    Datino T, Macle L, Qi XY, Maguy A, Comtois P, Chartier D, et al. Mechanisms by which adenosine restores conduction in dormant canine pulmonary veins. Circulation. 2010;121:963–72.CrossRefGoogle Scholar
  11. 11.
    Macle L, Khairy P, Verma A, Weerasooriya R, Willems S, Arentz T, et al. Adenosine following pulmonary vein isolation o target dormant conduction elimination (ADVICE): methods and rationale. Can J Cardiol. 2012;28:184–90.CrossRefGoogle Scholar
  12. 12.
    Kobori A, Shizuta S, Inoue K, Kaitani K, Morimoto T, Nkazawa Y, et al. Adenosine triphosphate-guided pulmonary vein isolation for atrial fibrillation: the Unmasking Dormant Electrical Reconduction by Adenosine TriPhosphate (UNDER-ATP) trial. Eur Heart J. 2015;36:3276–87.PubMedGoogle Scholar
  13. 13.
    Curtis AB, Belardinelli L, Woodart DA, Brown CS, Conti JB. Induction of atrioventricular node reentrant tachycardia with adenosine: differential effect of adenosine on fast and slow atrioventricular node pathways. J Am Coll Cardiol. 1997;30:1778–84.CrossRefGoogle Scholar
  14. 14.
    Dougherty AH, Gilman JK, Wiggins S, et al. Provocation of atrioventricular reentry tachycardia: a paradoxical effect of adenosine. Pacing Clin Electrophysiol. 1993;16:8–12.CrossRefGoogle Scholar
  15. 15.
    Vora A, Lokhandwala Y. Adenosine-induced tachycardia: what is the mechanism? J Cardiovasc Electrophysiol. 2000;11:491–2.CrossRefGoogle Scholar
  16. 16.
    Garratt CJ, O’Nunain S, Griffith MJ, Connelly DT, Rowland E, Ward DE, et al. Effects of intravenous adenosine in patients with preexcited junctional tachycardias: therapeutic efficacy and incidence of proarrhythmic events. Am J Cardiol. 1994;74:401–4.CrossRefGoogle Scholar
  17. 17.
    Orebaugh SL, Handy M. Intravenous adenosine therapy accelerating rate of paroxysmal supraventricular tachycardia. Am J Emerg Med. 1992;10:326–30.CrossRefGoogle Scholar
  18. 18.
    Ertan C, Atar I, Gulmez O, Atar A, Ozgul A, Aydinalp A, et al. Adenosine induced ventricular arrhythmias in patients with supraventricular tachycardias. Ann Noninvasive Electrocardiol. 2008;13:386–90.CrossRefGoogle Scholar
  19. 19.
    Misra D, Van Tosh A, Schweitzer P. Adenosine induced monomorphic ventricular tachycardia. Pacing Clin Electrophysiol. 2000;23:1044–6.CrossRefGoogle Scholar
  20. 20.
    DiMarco JP, Miles W, Akhtar M, Milstein S, Sharma AD, Platia E, et al. Adenosine for paroxysmal supraventricular tachycardia: dose ranging and comparison with verapamil. Assessment in placebo-contrSzent-Guorgyi. Olled, multicenter trials. The Adenosine for PSVT Study Group. Ann Intern Med. 1990;113:104–10.CrossRefGoogle Scholar
  21. 21.
    Tan HL, Spekhorst HHM, Peters RJG, Wilde AAM. Adenosine induced ventricular arrhythmias in the emergency room. Pacing Clin Electrophysiol. 2001;24:450–5.CrossRefGoogle Scholar
  22. 22.
    Biaggioni I, Killian TJ, Mosqueda-Garcia R, Robertson RM, Robertson D. Adenosine increases sympathetic nerve traffic in humans. Circulation. 1991;83:1668–75.CrossRefGoogle Scholar
  23. 23.
    Wit AL, Rosen MR. After depolarizations and triggered activity. In: Fozzard HA, et al., editors. The heart and cardiovascular system. New York: Raven Press; 1986. p. 1449–90.Google Scholar
  24. 24.
    Argentieri TM, Frame LH, Colatsky TJ. Electrical properties of canine subendocardial Purkinje fibers surviving in 1-day-old experimental myocardial infarction. Circ Res. 1990;66:123–34.CrossRefGoogle Scholar
  25. 25.
    Strickberger SA, Man KC, Daoud EG, Goyal R, Brinkman K, Knight BP, et al. Adenosine-induced atrial arrhythmia: a prospective analysis. Ann Intern Med. 1997;127:417–22.CrossRefGoogle Scholar
  26. 26.
    Isa-Param R, Perez-Castellano N, Villacastin J, Moreno J, Salinas J, Alonso R, et al. Inducibility of atrial arrhythmias after adenosine and isoproterenol infusion in patients referred for atrial fibrillation ablation. Rev Esp Cardiol. 2006;59:559–66.CrossRefGoogle Scholar
  27. 27.
    Corbisiero R, Kabell G, Cook JR, Fitzgerald TF, Kirchhoffer JB. Effects of adenosine on local stimulus-response latency and induction of atrial fibrillation by premature stimuli. Pacing Clin Electrophysiol. 1999;22:1378–85.CrossRefGoogle Scholar
  28. 28.
    Raviña T, Raviña P, Suárez M. Inestabilidad auricular tras adenosina. Rev Esp Cardiol. 2004;57:594–5.CrossRefGoogle Scholar
  29. 29.
    Arora R, Verheule S, Scott L, Navarrete A, Katari V, Wilson E, et al. Arrhythmogenic substrate of the pulmonary veins assessed by high-resolution optical mapping. Circulation. 2003;107:1816–21.CrossRefGoogle Scholar
  30. 30.
    Dixit S, Gerstenfeld EP, Callans DJ, Marchlinski FE. Mechanisms underlying sustained firing from pulmonary veins: evidence from pacing maneuvers and pharmacological manipulation. Pacing Clin Electrophysiol. 2004;27:1120–9.CrossRefGoogle Scholar
  31. 31.
    Marchlinski F, Callans D, Dixit S, Gerstenfeld E, Rho R, Ren JF, et al. Efficacy and safety of targeted focal ablation versus PV isolation assisted by magnetic electroanatomic mapping. J Cardiovasc Electrophysiol. 2003;14:358–65.CrossRefGoogle Scholar
  32. 32.
    Macle L, Khairy P, Weerasooriya R, Novak P, Verma A, Willems S, et al. Adenosine-guided pulmonary vein isolation for the treatment of the paroxysmal atrial fibrillation: an international multicenter, randomized superiority trial. Lancet. 2015;386:672–9.CrossRefGoogle Scholar
  33. 33.
    Mc Lellan AJ, Kumar S, Smith C, Morton JB, Kalman JM, Kistler PM. The role of adenosine following pulmonary vein isolation in patients undergoing catheter ablation for atrial fibrillation: a systematic review. J Cardiovasc Electrophysiol. 2013;24:724–51.Google Scholar
  34. 34.
    Hernandez J, Ribeiro JA. Excitatory actions of adenosine on ventricular automaticity. Trends Pharmacol Sci. 1996;17:141–4.CrossRefGoogle Scholar
  35. 35.
    Hernandez J, Laorden ML, Ruiz F, Ribeiro JA. Effects of adenosine and its analogues on ventricular automaticity induced by a local injury: role of catecholamines and of cyclic AMP. Arch Int Pharmacodyn Ther. 1989;297:49–59.PubMedGoogle Scholar
  36. 36.
    Shah CP, Gupta AK, Thakur RK, et al. Adenosine induced ventricular fibrillation. Indian Heart J. 2001;53:208–10.PubMedGoogle Scholar
  37. 37.
    Gupta AK, Shah CP, Maheshwari A, Thakur RK, Hayes OW, et al. Adenosine induced ventricular fibrillation in Wolf-Parkinson-White syndrome. Pacing Clin Electrophysiol. 2002;25:477–80.CrossRefGoogle Scholar
  38. 38.
    Rajkumar CA, Qureshi N, Siong NGF, Panoulas VF, Lim PB. Adenosine induced ventricular fibrillation in a structurally normal heart: a case report. J Med Case Rep. 2017;11:21.CrossRefGoogle Scholar
  39. 39.
    Smith JR, Goldberger JJ, Kadish AH. Adenosine induced polymorphic ventricular tachycardia in adults without structural heart disease. Pacing Clin Electrophysiol. 1997;20:743–5.CrossRefGoogle Scholar
  40. 40.
    Parham WA, Mehdirad AA, Biermann KM, Fredman CS. Adenosine induced ventricular fibrillation in a patient with stable ventricular tachycardia. J Interv Card Electrophysiol. 2001;5:71–4.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Simona Căinap
    • 1
  1. 1.“Iuliu Hatieganu University of Medicine and Pharmacy”, Pediatric Clinic No 2, Pediatric CardiologyCluj-NapocaRomania

Personalised recommendations