Skip to main content
SpringerLink
Log in

Extracardiac effects of cardiac glycosides

  • Conference paper
Cardiac Glycosides 1785–1985

Abstract

The extracardiac effects of cardiac glycosides which are of greatest interest to us are those that involve an interaction of these drugs with neural tissue, and result in changes in cardiovascular function. In this category, we are especially interested in interactions of cardiac glycosides with two neural sites, namely, reflexogenic areas of the cardiovascular system, and the central nervous system (i. e., CNS sites that control sympathetic outflow). In this review we will discuss evidence documenting an interaction of cardiac glycosides with reflexogenic areas and with CNS sites that influence autonomic nervous system outflow. This will be followed by a discussion of evidence indicating that neuroexcitatory effects of cardiac glycosides play an important role in the cardiovascular effects of these agents. Interaction of cardiac glycosides with reflexogenic sites can explain many of the therapeutic effects of these drugs such as their antiarrhythmic effects and effects on preload, afterload, and renal function in patients with congestive heart failure. Interaction of cardiac glycosides with the CNS, specifically CNS sites that influence sympathetic outflow, can explain in part the ventricular tachyarrhythmias that occur with toxic doses of these agents.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
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.

References

  1. Abiko Y, Mukahira K, Tanabe T (1964) Blockade with dichloroisoproterenol (DCI) of the sympathetic factor of strospeside-induced bradycardia in cats. Jap J Pharmacol 14: 212–231

    Article  Google Scholar 

  2. Arnold SB, Byrd RC, Meister W, Melmon K, Cheitlin MD, Bristoro JD, Parmley WW, Chatterjee K (1980) Long term digitalis therapy improves left ventricular function in heart failure. New Eng J Med 303: 1443–1448

    Article  PubMed  CAS  Google Scholar 

  3. Blumberg JM, Hayes JG, Stevens M, Sullivan G, Killip T (1973) Digitalis in treatment of ventricular extrasystoles in the otherwise normal heart. Circulation 48 (Suppl IV): 8

    Google Scholar 

  4. Brooks WW, Verner RL, Lown B (1979) Digitalis drugs and vulnerability to ventricular fibrillation. Eur J Pharmacol 57: 69–78

    Article  PubMed  CAS  Google Scholar 

  5. Caldwell RW, Nash CB (1976) Pharmacological studies of a new 4-aminosugar cardiac glycoside (ASI-222). J Pharmacol Exp Ther 197: 19–26

    PubMed  CAS  Google Scholar 

  6. Caldwell RW, Nash CB (1977) Comparison of the therapeutic index (TI) of aminosugar cardiac glycosides with digoxin (D). Fed Proc 36: 3705

    Google Scholar 

  7. Chai CY, Wang HH, Hoffman BF, Wang SC (1967) Mechanisms of bradycardia induced by digitalis substances. Amer J Physiol 212: 26–34

    PubMed  CAS  Google Scholar 

  8. Covit AB, Schaer GL, Sealey JE, Laragh JH, Cody RJ (1983) Suppression of the renin-angiotensin system by intravenous digoxin in chronic congestive heart failure. Am J Med 75: 445–447

    Article  PubMed  CAS  Google Scholar 

  9. Evans DE, Gillis RA (1975) Effect of ouabain and its interaction with diphenylhydantoin on cardiac arrhythmias induced by hypothalamic stimulation. J Pharmacol Exp Ther 195: 557–586

    Google Scholar 

  10. Ferrari A, Gregorini L, Ferrari MC, Preti L, Mancia G (1981) Digitalis and baroreceptor reflexes in man. Circulation 63: 279–285

    Article  PubMed  CAS  Google Scholar 

  11. Garan H, Powers ER, Powell WJ Jr (1974) Dependence of the neurogenic vascular resistance effect of digitalis on the background level of sympathetic activity in skeletal muscle. Fed Proc 33: 584

    Google Scholar 

  12. Garan H, Smith TW, Powell WJ Jr (1974) The central nervous system as a site of action for the coronary vasoconstrictor effect of digoxin. J Clin Invest 54: 1365–1372

    Article  PubMed  CAS  Google Scholar 

  13. Garvey HL (1972) Role of the autonomic nervous system in digitalis intoxication. In: Bajusz E, Rona G (eds) Recent Advances in Studies on Cardiac Structure and Metabolism, Vol 1. University Park Press, London, pp 563–573

    Google Scholar 

  14. Gatti PJ, Dias Souza J, DaSilva AMT, Quest JA, Gillis RA (1985) Chemical stimulation of the area postrema induces cardiorespiratory changes in the cat. Brain Res 346: 115–123

    Article  PubMed  CAS  Google Scholar 

  15. Gillis RA (1969) Cardiac sympathetic nerve activity: Changes induced by ouabain and propranolol. Science 166: 508–510

    Article  PubMed  CAS  Google Scholar 

  16. Gillis RA, Dias Souza J, Gatti PJ (1985) Mechanism of the ventricular tachyarrhythmias that occur after topical application of kainic acid to the area postrema of the cat. Neurosci Absts 11: 191

    Google Scholar 

  17. Gillis RA, Dionne RA, Standaert FG (1972) Suppression by clonidine (St-155) of cardiac arrhythmias induced by digitalis. J Pharmacol Exp Ther 182: 218–226

    PubMed  CAS  Google Scholar 

  18. Gillis RA, Jolson H, Thibodeaux H, Levitt B (1975) Antagonism of deslanoside-induced cardiotoxicity by combined nicotinic and muscarinic blockade of autonomic ganglia. J Pharmacol Exp Ther 195: 126–132

    PubMed  CAS  Google Scholar 

  19. Gillis RA, McClellan JR, Sauer TS, Standaert FG (1971) Depression of cardiac sympathetic nerve activity by diphenylhydantoin. J Pharmacol Exp Ther 179: 599–610

    PubMed  CAS  Google Scholar 

  20. Gillis RA, Quest JA (1980) The role of the nervous system in the cardiovascular effects of digitalis. Pharmacol Rev 31: 19–97

    Google Scholar 

  21. Gillis RA, Quest JA, Standaert FG (1969) Depression by reflexes of the pressor and cardiotoxic responses to ouabain. J Pharmacol Exp Ther 170: 294–302

    PubMed  CAS  Google Scholar 

  22. Gillis RA, Quest JA, Thibodeaux H, Clancy MM, Evans DE (1975) Neural mechanisms involved in acetylstrophanthidin-induced bradycardia. J Pharmacol Exp Ther 193: 336–345

    PubMed  CAS  Google Scholar 

  23. Gillis RA, Raines A, Sohn YJ, Levitt B, Standaert FG (1972) Neuroexcitatory effects of digitalis and their role in the development of cardiac arrhythmias. J Pharmacol Exp Ther 183: 154–168

    PubMed  CAS  Google Scholar 

  24. Gillis RA, Thibodeaux H, Barr L (1974) Antiarrhythmic properties of chlordiazepoxide. Circulation 49: 272–282

    Article  PubMed  CAS  Google Scholar 

  25. Gilmore JP, Zucker IH (1979) Activity of atrial receptors under normal and pathological states. In: Hainsworth R, Kidd C, Linden RJ (eds) Cardiac Receptors, Cambridge Univ Press, New York, pp 139–156

    Google Scholar 

  26. Hamlin NP, Willerson JT, Garan H, Powell WJ Jr (1974) The neurogenic vasoconstrictor effect of digitalis on coronary vascular resistance. J Clin Invest 53: 288–296

    Article  PubMed  CAS  Google Scholar 

  27. Heike CJ, Gillis RA (1978) Centrally mediated protective effects of dopamine agonists on digitalis-induced ventricular arrhythmias. J Pharmacol Exp Ther 207: 263–270

    Google Scholar 

  28. Imamura T, Takeshita A, Ashihara T, Yamamoto K, Hoka S, Makamura M (1985) Digitalis-induced augmentation of cardiopulmonary baroreflex control of forearm vascular resistance. Circulation 71: 11–16

    Article  PubMed  CAS  Google Scholar 

  29. Kao A, Kriett JM, Tobler HG, Detloff BLS, Pritzker MR, Benson DW, Benditt DG (1984) Bromocriptine treatment of digitalis-induced ventricular tachyarrhythmias: Studies in a canine model. J Amer Coll Cardiol 4: 1188–1194

    Article  CAS  Google Scholar 

  30. Leachman RD, Cokkinos DVP, Cabrera R, Leatherman LL, Rochelle DG (1971) Response of the transplanted, denervated human heart to cardiovascular drugs. Amer J Cardiol 27: 272–276

    Article  PubMed  CAS  Google Scholar 

  31. Lown B, Graboys TB, Podrid PJ, Cohen BH, Stockman MB, Gaughan CE (1977) Effect of a digitalis drug on ventricular premature beats. N Engl J Med 296: 301–306

    Article  PubMed  CAS  Google Scholar 

  32. Mason DT, Zelis R, Amsterdam EA (1972) Unified concept of the mechanism of action of digitalis: Influence of ventricular function and cardiac disease on hemodynamic response to fundamental contractile effect. In: Marks BH, Weissler AM (eds) Basic and Clinical Pharmacology of Digitalis. Chales C Thomas, Springfield, Ill, pp 1206–1229

    Google Scholar 

  33. McLain PL (1969) Effects of cardiac glycosides on spontaneous efferent activity in vagus and sympathetic nerves of cats. Int J Neuropharmacol 8: 379–387

    Article  PubMed  CAS  Google Scholar 

  34. Pace DG, Gillis RA (1976) Neuroexcitatory effects of digoxin in the cat. J Pharmacol Exp Ther 199: 583–600

    PubMed  CAS  Google Scholar 

  35. Puryear SK, Nash CB, Caldwell RW (1981) Effect of cardiac 13-adrenergic blockade or denervation on cardiotoxicity of digoxin and an aminosugar cardenolide. J Cardiovasc Pharmacol 3: 113–127

    Article  PubMed  CAS  Google Scholar 

  36. Quest JA, Gillis RA (1971): Carotid sinus reflex changes produced by digitalis. J Pharmacol Exp Ther 177: 650–661

    PubMed  CAS  Google Scholar 

  37. Quest JA, Gillis RA (1974) Effect of digitalis on carotid sinus baroreceptor activity. Circ Res 35: 247–255

    Article  CAS  Google Scholar 

  38. Quest JA, Rowles GS, Bhat HB, Gillis RA (1976) Effect of dihydroouabain on vascular tone of the perfused canine hindlimb. J Pharmacol Exp Ther 199: 255–261

    PubMed  CAS  Google Scholar 

  39. Reid JL, Wing LMH, Mathias CJ, Frankel HL, Neill E (1977) The central hypotensive effect of clonidine. Studies in tetraplegic subjects. Clin Pharmacol Ther 21: 375–381

    PubMed  CAS  Google Scholar 

  40. Schinz A, Klein G, Blomer H (1977) Time sequence of direct vascular and inotropic effects following intravenous administration of digixon in normal man. Int J Clin Pharmacol 15: 189–193

    CAS  Google Scholar 

  41. Sleight P, Lall A, Muers M (1969) Reflex cardiovascular effects of epicardial stimulation by acetylstrophanthidin in dogs. Cire Res 25: 705–711

    Article  CAS  Google Scholar 

  42. Somberg JC, Kuhlman JE, Smith TW (1981) Localization of the neurally mediated coronary vasoconstrictor properties of digitalis in the cat. Circ Res 49: 226–233

    Article  PubMed  CAS  Google Scholar 

  43. Somberg JC, Smith TW (1979) Localization of the neurally mediated arrhythmogenic properties of digitalis. Science 204: 321–323

    Article  PubMed  CAS  Google Scholar 

  44. Stark JJ, Sanders CA, Powell WJ Jr (1972) Neurally mediated and direct effects of acetylstrophanthidin on canine skeletal muscle vascular resistance. Circ Res 30: 274–282

    Article  PubMed  CAS  Google Scholar 

  45. Thames MD (1979) Acetylstrophanthidin-induced reflex inhibition of canine renal sympathetic nerve activity mediated by cardiac receptors with vagal afferents. Circ Res 44: 8–15

    Article  PubMed  CAS  Google Scholar 

  46. Thames MD, Miller BD, Abboud FM (1982) Sensitization of vagal cardiopulmonary baroreflex by chronic digoxin. Am J Physiol 243 (Heart Circ Physiol 12): H 815-H 818

    Google Scholar 

  47. Thames MD, Vaickman LA, Abboud FM (1980) Sensitization of cardiac receptors (vagal afferents) by intracoronary acetylstrophanthidin. Am J Physiol (Heart Circ Physiol 8): H 628-H 635

    Google Scholar 

  48. Thron CD, Riancho JA, Borison HL (1984) Lack of protection against ouabain cardiotoxicity after chronic abtation of the area postrema in cats. Exper Neurol 85: 574–583

    Article  CAS  Google Scholar 

  49. Watanabe AM, Judy WV, Cardon PV (1974) Effect of L-dopa on blood pressure and sympathetic nerve activity after decarboxylase inhibition in cats. J Pharmacol Exp Ther 188: 107–113

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Schools of Medicine and Dentistry, Georgetown University, Washington, D. C., USA

    Richard A. Gillis & J. A. Quest

  2. Schools of Medicine and Dentistry, Georgetown University, 3900 Reservoir Rd., N. W., Washington, D. C., 20007, USA

    Richard A. Gillis

Authors
  1. Richard A. Gillis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. A. Quest
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medizinische Klinik I, Klinikum Großhadern der Universität München, Marchioninistraße 15, 8000, München 70, West Germany

    Erland Erdmann

  2. Institut für Pharmakologie, Universität Düsseldorf, Moorenstraße 5, 4000, Düsseldorf, West Germany

    K. Greef

  3. Biophysik Institut, Aarhus Universitet, Universitetparken, 8000, Aarhus, Denmark

    J. C. Skou

Rights and permissions

Reprints and permissions

Copyright information

© 1986 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Gillis, R.A., Quest, J.A. (1986). Extracardiac effects of cardiac glycosides. In: Erdmann, E., Greef, K., Skou, J.C. (eds) Cardiac Glycosides 1785–1985. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-662-11292-2_47

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-11292-2_47

  • Publisher Name: Steinkopff, Heidelberg

  • Print ISBN: 978-3-662-11294-6

  • Online ISBN: 978-3-662-11292-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation