Skip to main content
SpringerLink
Log in

Use Dependence and Reverse Use Dependence of Antiarrhythmic Agents: Pro- and Antiarrhythmic Actions

  • Chapter
Antiarrhythmic Drugs

Abstract

The normal heart beat starts at regular intervals (600–1000 ms) in the SA node, then propagates through the atria to enter the AV node, where conduction is slow. With some delay it enters the His-Purkinje system which quickly activates the ventricular myocardium. When activation of the heart deviates from this normal activation sequence an arrhythmia results. The most serious arrhythmias are those where the normal pumping function of the heart is jeopardized like in fibrillation and tachycardia. In fibrillation, there exists no synchronization between the heart cells so that the pumping of blood stops, while in tachycardia the heart contracts so frequently that it contracts before it has properly filled. As a result cardiac output is very low. Because of the seriousness of these two arrhythmias, I concentrate on the electropharmacology of agents that interfere with tachycardias and fibrillation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. Anderson KP, Walker R, Dustman T, Lux RL, Ershler PR, Kates RE, Urie PM (1989) Rate-related electrophysiologic effects of long-term administration of amiodarone on canine ventricular myocardium in vivo. Circulation 79: 948–958

    Article  PubMed  CAS  Google Scholar 

  2. Anno T, Bennett PB, Hondeghem LM, Snyders DJ (199o) Activation unblock of cardiac Na channels without opening. Biophys J 57:107 a

    Google Scholar 

  3. Antzelevitch C, Litovsky SH, Lukas A (199o) Epicardium versus endocardium: electrophysiology and pharmacology. In: Zipes DP, Jalife J (eds) Cardiac electrophysiology. From cell to beside. Saunders, Philadelphia, pp 386–395

    Google Scholar 

  4. Balser JR, Bennett PB, Hondeghem LM, Roden DM (1991) Suppression of time-dependent outward current in guinea pig ventricular myocytes: actions of quinidine and amiodarone. Circ Res 69:519–529

    Google Scholar 

  5. Beeler GW, Reuter H (1977) Reconstruction of the action potential of ventricular myocardial fibres. J Physiol (Lond) 268: 177–210

    CAS  Google Scholar 

  6. Bennett P, McKinney L, Begenisich T, Kass RS (1986) Adrenergic modulation of the delayed rectifier potassium channel in calf cardiac Purkinje fibers. Biophys J 49: 839–848

    Article  PubMed  CAS  Google Scholar 

  7. Carlsson L, Almgren 0, Duker G (1990) QTU-Prolongation and torsades de pointes induced by putative class III antiarrhythmic agents in the rabbit: etiology and interventions. J Cardiovasc Pharmacol 16: 276–285

    Article  PubMed  CAS  Google Scholar 

  8. Carlsson L, Abrahamsson C, Almgren O, Lundberg C, Duker G (1991) Prolonged action potential duration and positive inotropy induced by a novel class III antiarrhythmic agent H234/09 (almokalant) in isolated human ventricular muscle. J Cardiovasc Pharmacol 18: 882–887

    Article  PubMed  CAS  Google Scholar 

  9. Carmeliet E (1993) Use-dependent block and use-dependent unblock of the delayed rectifier K+ current by almokalant in rabbit ventricular myocytes. Circ Res 73:857–868

    Google Scholar 

  10. Chen CM, Gettes LS, Katzung BG (1975) Effect of lidocaine and quinidine on steady state characteristics and recovery kinetics of (dV/dt)max in guinea pig ventricular myocardium. Circ Res 37: 20–29

    Article  PubMed  CAS  Google Scholar 

  11. Courtney KR (1975) Mechanism of frequecy-dependent inhibition of sodium currents in frog myelinated nerve by the lidocaine derivative GEA 968. JPET 195:225–236

    Google Scholar 

  12. Duker G, Almgren O, Carlsson L (1992) Electrophysiologic and hemodynamic effects of H 234/09 (almokalant), quinidine, and (+) sotalol in the anesthetized dog. J Cardiovasc Pharmacol 20:4558–465

    Google Scholar 

  13. El-Sherif N, Fozzard HA, Hank DA (1992) Dose-dependent modulation of the cardiac sodium channel by sea anemone toxin ATXII. Circ Res 70: 285–301

    Article  PubMed  CAS  Google Scholar 

  14. Escande D, Coulombe A, Faivre JF (1987) Two types of transient outward currents in adult human atrial cells. Am J Physiol 252:H142 – H 148

    Google Scholar 

  15. Harvey RD, Clark CD, Hume JR (1990) Chloride current in mammalian cardiac myocytes — novel mechanism for autonomic regulation of action potential duration and resting membrane potential. J Physiol (Lond) 95: 1077

    CAS  Google Scholar 

  16. Hashimoto K, Ochi R, Inu J, Miura Y (1980) The ionic mechanism of prolongation of action potential duration of cardiac ventricular muscle by anthopleurin-A and its relationship to the inotropic effect. J Pharmacol Exp Ther 215: 479–485

    Google Scholar 

  17. Heistracher P (1971) Mechanism of action of antifibrillatory drugs. NaunynSchmiedebergs Arch Pharmacol 269: 199–212

    Article  CAS  Google Scholar 

  18. Hess P, Lansman JB, Tsien RW (1984) Different modes of Ca channel gating behavior favored by dihydropyridine Ca agonists and antagonists. Nature 311: 538–544

    Article  PubMed  CAS  Google Scholar 

  19. Hille B (1977) Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol 69:497–515

    Google Scholar 

  20. Hiraoka M, Sunami A, Fan Z, Sawanobori T (1992) Multiple ionic mechanisms of early afterdepolarizations in isolated ventricular myocytes from guinea pig hearts. Ann NY Acad Sci 64: 33

    Article  Google Scholar 

  21. Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol (Lond) 117: 500–544

    CAS  Google Scholar 

  22. Hondeghem LM (1987) Antiarrhythmic agents: modulated receptor applications. Circulation 75:514–520

    Google Scholar 

  23. Hondeghem LM (1991) Ideal antiarrhythmic agents: Chemical defibrillators. J Cardiovasc Electrophysiol 2: 169–177

    Google Scholar 

  24. Hondeghem LM, Bennett PB (1989) Model of antiarrhythmic drug action. In: Hondeghem LM (ed) Molecular and cellular mechanisms of antiarrhythmic agents. Futura, Mount Kisco, pp 201–239

    Google Scholar 

  25. Hondeghem LM, Katzung BG (1977) Time-and voltage-dependent interactions of anti-arrhythmic drugs with cardiac sodium channels. Biochim Biophys Acta 472:373–398

    Google Scholar 

  26. Hondeghem LM, Matsubara T (1990) Quinidine blocks cardiac sodium channels during opening and slow inactivation in guinea pig papillary muscle. Br J Pharmacol 93:311–313

    Google Scholar 

  27. Hondeghem LM, Snyders DJ (1990) Class III antiarrhythmic agents have a lot of potential, but a long way to go: reduced effectiveness and dangers of reverse use-dependence. Circulation 81: 686–690

    Article  PubMed  CAS  Google Scholar 

  28. Hondeghem LM, Mason JW (1993) Agents used in cardiac arrhythmias. In: Katzung BG (ed) Basic and clinical pharmacology, 4`h edn. Appleton and Lange Medical, Norwalk, pp 165–182

    Google Scholar 

  29. Huang L, Moran N, Ehrenstein G (1982) Batrachotoxin modifies the gating kinetics of sodium channels in internally perfused neuroblastoma cells. Proc Natl Acad Sci USA 79: 2082–2085

    Article  PubMed  CAS  Google Scholar 

  30. Hume JR, Harvey RD (1991) Chloride conductance pathways in heart. Am J Physiol 261:C399–C412

    Google Scholar 

  31. Isenberg G, Ravens U (1984) Th effects of anemonia sulvata toxin (ATX II) on membrane currents of isolated mammalina myocytes. J Physiol 357:127–149

    Google Scholar 

  32. January CT, Riddle JM, Salata JJ (1988) A model for early afterdepolarizations: induction with the Ca2+ channel agonist Bay K8644. Circ Res 62 (3): 563–71

    Article  PubMed  CAS  Google Scholar 

  33. Johnson EA, McKinnon MG (1957) The differential effect of quinidine and pyrilamine on the myocardial action potential at various rates of stimulation. JPET 120: 460–468

    CAS  Google Scholar 

  34. Kodoma I, Toyama J, Takanaka C, Yamada K (1987) Block of activated and inactivated sodium channels by class I antiarrhythmic drugs studied by using the maximum upstroke velocity (Vmax) of action potential in guinea pig cardiac muscles. J Mol Cell Cardiol 19:367–377

    Google Scholar 

  35. Kohlhardt M, Froke U, Herzig JW (1986) Modification of single channel cardiac Na+ channels by DPI 201–106. J Membr Biol 89: 163–172

    Article  PubMed  CAS  Google Scholar 

  36. Kojima M, Ban T, Sada H (1982) Effects of disopyramide on the maximum rate of rise of action potential (Vm) in guinea pig papillary muscles. Jpn J Pharmacol 32: 91–102

    Article  PubMed  CAS  Google Scholar 

  37. Lee KS (1992) Ibutilide, a new compound with potent class III antiarrhythmic activity, activates a slow inward Na+ current in guinea pig ventricular cells. J Pharmacol Exp Ther 262: 99–108

    PubMed  CAS  Google Scholar 

  38. Mason JW, Hondeghem LM, Katzung BG (1984) Block of inactivated sodium channels and of depolarization-induced automaticity in guinea pig papillary muscle by amiodarone. Circ Res 55:277–285

    Google Scholar 

  39. Matsubara T, Clarkson CW, Hondeghem LM (1987) Lidocaine blocks open and inactivated cardiac sodium channels. Naunyn Schmiedebergs Arch Pharmacol 336: 224–231

    Article  PubMed  CAS  Google Scholar 

  40. Nilius B, Boldt W, Benndorf K (1986) Properties of aconitine-modified sodium channels in single cells of mouse ventricular myocardium. Gen Physiol Biophys 5: 473

    PubMed  CAS  Google Scholar 

  41. Nilius B, Vereecke J, Carmeliet E (1989) Properties of the bursting Na+ channel in the presence of DPI 201–106 in guinea pig ventricular myocytes. Pflugers Arch 234–241

    Google Scholar 

  42. Noble D, Noble SJ, Bett GCL et al. (1991) The role of the sodium-calcium exchange during the cardiac action potential. Ann NY Acad Sci 639: 334

    Article  PubMed  CAS  Google Scholar 

  43. Noble D (1994) The ionic basis of the heartbeat and cardiac arrhythmias. In: Singh BN, Wellens HJJ, Hiraoka M (eds) Electropharmacological control of cardiac arrhythmias. Futura, Mount Kisco, pp 3–20

    Google Scholar 

  44. Noma A (1983) ATP-regulated K+ channels in cardiac muscle. Nature 305: 147–148

    Article  PubMed  CAS  Google Scholar 

  45. Pelzer D, Trautwein W, McDonald TF (1982) Calcium channel block and recovery from block in mammalian ventricular muscle treated with organic channel inhibitors. Pflugers Arch 394: 97–105

    Article  PubMed  CAS  Google Scholar 

  46. Roden DM, Hoffman BF (1985) Action potential prolongation and induction of abnormal automaticity by low quinidine concentrations in canine Purkinje fibers: relationship to potassium and cycle lenght. Circ Res 56: 857–867

    Article  PubMed  CAS  Google Scholar 

  47. Roden DM, Bennett PB, Snyders DJ, Balser JR, Hondeghem LM (1988) Quinidine delays IK activation in guinea pig ventricular myocytes. Circ Res 62: 1055–1058

    Article  PubMed  CAS  Google Scholar 

  48. Sager PT, Uppal P, Follmer C, Antimisiaris M, Pruitt C, Singh BN (1993) Frequency-dependent electrophysiologic effects of amiodarone in humans. Circulation 88: 1063–1071

    Google Scholar 

  49. Sakman B, Noma A, Trautwein W (1983) Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart. Nature 3o3: 250 – 253

    Google Scholar 

  50. Sanguinetti MC, Jurkiewicz NK (1990) Two components of cardiac delayed rectifier K+ current: differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol 96: 194–215

    Article  Google Scholar 

  51. Snyders DJ, Hondeghem LM (1990) Effects of quinidine on the sodium current of guinea pig ventricular myocytes. Evidence for a drug-associated rested state with altered kinetics. Circ Res 66: 565–579

    Google Scholar 

  52. Tsien RW, Bean BP, Hess P, Lansman JB, Nilius B, Nowycky MC (1986) Mechanisms of calcium channel modulation by ß-adrenergic agents and dihydropyridine calcium agonists. 18: 691–710

    CAS  Google Scholar 

  53. van Bogaert PP, Goethals M, Simoens C (1990) Use- and frequency-dependent blockade by UL-FS 49 of if pacemaker current in sheep cardiac Purkinje fibres. Eur J Pharmacol 187: 241–256

    Article  PubMed  Google Scholar 

  54. Weidmann S (1995) Effects of calcium ions and local anesthetics on electrical properties of Purkinje fibres. J Physiol (Lond) 129:568–582

    Google Scholar 

Download references

Authors
  1. L. M. Hondeghem
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medizinische Klinik und Poliklinik, Innere Medizin C, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Straße 33, D-48129, Münster, Germany

    Günter Breithardt , Wilhelm Haverkamp  & Gerhard Hindricks ,  & 

  2. Dept. of Cardiological Sciences, St. George’s Hospital Medical School Cranmer Terrace, SW17 ORE, London, UK

    A. John Camm

  3. Department of Medicine, O’Connor Hospital, 2100 Forest Avenue, Suite 110, 95128, San Jose, CA, USA

    Mohammad Shenasa

  4. Department of Cardiology and Angiology, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Straße 33, D-48129, Münster, Germany

    Martin Borggrefe

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Hondeghem, L.M. (1995). Use Dependence and Reverse Use Dependence of Antiarrhythmic Agents: Pro- and Antiarrhythmic Actions. In: Breithardt, G., Borggrefe, M., Camm, A.J., Shenasa, M., Haverkamp, W., Hindricks, G. (eds) Antiarrhythmic Drugs. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85624-2_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-85624-2_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-85626-6

  • Online ISBN: 978-3-642-85624-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation