Skip to main content
SpringerLink
Log in

Dysrhythmias caused by histamine release in guinea pig and human hearts

Rhythmusstörungen durch Histaminfreisetzung im Herz von Meerschweinchen und Mensch

  • 3. Effects Of Histamine On The Cardiovascular And Respiratory System
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Summary

Histamine is released into the systemic circulation during anaphylaxis, by drugs and by surgical procedures. Studies in animal models have conclusively demonstrated that released cardiac histamine is a major mediator of arrhythmias that occur during anaphylaxis and following the administration of histamine-releasing drugs. Several lines of evidence suggest a similar arrhythmogenic role for cardiac histamine in humans: (1) The human heart is rich in histamine; (2) cardiac histamine can be readily released from human heartin vitro by therapeutic concentrations of drugs; (3) histamine has potent arrhythmogenic effects on the human heartin vitro.

Arrhythmogenic effects of histamine include enhancement of normal automaticity, induction of abnormal automaticity, induction of triggered tachyarrhythmias, depression of atrioventricular conduction, and increase in the vulnerability of the ventricles to fibrillation. A combination of H1 and H2 antihistamines is needed to block the arrhythmogenic effects of histamine. Certain arrhythmogenic effects of histamine (e.g. induction of slow responses and delayed afterdepolarizations) can also be blocked by drugs which inhibit the influx of cations through slow channels. In contrast, the commonly-used drug digitalis potentiates the arrhythmogenic effects of histamine.

We propose that histamine release produced by drugs and surgical procedures may be an overlooked factor in fatal cardiac arrhythmias. Experimental studies suggest that selective pharmacological methods can be developed to block the arrhythmogenic effects of histamine.

Zusammenfassung

Während der Anaphylaxie durch Arzneimittel und chirurgische Eingriffe wird Histamin in den systemischen Kreislauf freigesetzt. Durch Tierstudien konnte eindeutig gezeigt werden, daß freigesetztes Histamin aus dem Herzen ein Hauptmediator für Arrhythmien ist, die während Anaphylaxie nach Gabe von histaminfreisetzenden Arzneimitteln auftreten. Verschiedene Gründe weisen auf eine ähnliche arrhythmogene Rolle für kardiales Histamin beim Menschen hin:

(1) Das menschliche Herz ist reich an Histamin; (2) kardiales Histamin kann vom menschlichen Herzenin vitro durch therapeutische Arzneimittelkonzetrationen schnell freigesetzt werden; (3) Histamin hat einen starken arrhythmogenen Effekt auf das menschliche Herzin vitro.

Arrhythmogene Effekte des Histamins schließen die Erhöhung der normalen Herztätigkeit, die Induktion einer abnormalen Herztätigkeit, die Induktion von verstärkten Tachyarrhythmien, die Verminderung arterioventrikulärer Reize und eine Erhöhung in der Empfindlichkeit der Ventrikel für Herzflimmern ein. Eine Kombination von H1-and H2-Antihistaminika ist notwendig, um die errhythmogenen Effekte des Histamins zu blockieren. Bestimmte arrhythmogene Effekte des Histamins (z.B. die Induktion von verlangsamten Reaktionen und verzögerten Nachdepolarisationen) können auch durch Arzneimittel blockiert werden, die den Einfluß von Kationen durch die langsamen Kanäle hemmen. Im Gegensatz dazu verstärkt das allgemein gebräuchliche Mittel Digitalis die arrhythmogenen Effekte des Histamins.

Wir vermuten, daß Histaminfreisetzung durch Arzneimittel und chirurgische Eingriffe ein häufig übersehener Faktor bei tödlichen Herzarrhythmien sein könnte. Experimentelle Studien legen nahe, daß selektive pharmakologische Methoden entwickelt werden können, um die arrhythmogenen Effekte des Histamins zu verhindern.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Allan G, Levi R (1981) Thromboxane and prostacyclin release during cardiac immediate hypersensitivity reactions in vitro. J Pharmacol Exp Ther 217:157–161

    Google Scholar 

  2. Burke JA, Levi R, Guo Z-G, Corey EJ (1982) Leukotrienes C4, D4 and E4: Effects on human and guinea pig cardiac preparations in vitro. J Pharmacol Exp Ther 221:235–241

    Google Scholar 

  3. Capurro N, Levi R (1973) Anaphylaxis in the isolated guinea pig heart: Selective inhibition by burimamide of the positive inotropic and chronotropic effects of released histamine. Brit J Pharmacol 48:620–628

    Google Scholar 

  4. Capurro N, Levi R (1975) The heart as a target organ in systemic allergic reactions: Comparison of cardiac anaphylaxis in vivo and in vitro. Circulation Res 36:520–528

    Google Scholar 

  5. Carmeliet E, Vereecke J (1969) Adrenaline and the plateau phase of the cardiac action potential. Pflueg Arch 313:300–315

    Google Scholar 

  6. Cranefield PF (1977) Action potentials, after potentials and arrhythmias. Circulation Res 41:415–423

    Google Scholar 

  7. Cranefield PF, Wit AL, Hoffman BF (1972) Conduction of the cardiac impulse III. Characteristics of very slow conduction. J Gen Physiol 59:227–246

    Google Scholar 

  8. Cranefield PF, Wit AL, Hoffman BF (1973) Genesis of cardiac arrhythmias. Circulation 47:190–204

    Google Scholar 

  9. Hoffman BF, Bigger JT (1980) Digitalis and allied cardiac glycosides. In: Gilman AG, Goodman LG, Gilman A. The pharmacological basis of therapeutics, 6th edn. Macmillan, New York, 729–760

    Google Scholar 

  10. Houki S (1973) Restoration effects of histamine on action potential in potassium-depolarized guinea-pig papillary muscle. Arch Int Pharmacodyn 206:113–120

    Google Scholar 

  11. Inui J, Imamura H (1976) Restoration by histamine of the calcium-dependent electrical and mechanical response in the guinea-pig papillary muscle partially depolarized by potassium. N–S Arch Pharmakol 294:261–269

    Google Scholar 

  12. James RGG, Arnold JMO, Allen JD, Pantridge JF, Shanks RG (1977) The effects of heart rate, myocardial ischemia and vagal stimulation on the threshold for ventricular fibrillation. Circulation 55:311–317

    Google Scholar 

  13. Ledda F, Mantelli L, Mugelli A (1976) Blockade by burimamide of the restorative effect of histamine in tetrodoxotoxintreated heart preparations. Brit J Pharmacol 57:247–249

    Google Scholar 

  14. Levi R (1972) Effects of exogenous and immunologically released histamine on the isolated heart: A quantitative comparison. J Pharmacol Exp Ther 182:227–238

    Google Scholar 

  15. Levi R, Allan G (1980) Histamine-mediated cardiac effects. In: Bristow M (ed) Drug-induced heart disease. Elsevier-North Holland Biomedical Press, Amsterdam, 377–395

    Google Scholar 

  16. Levi R, Burke JA, Corey EJ (1982a) SRS-A, leukotrienes and immediate hypersensitivity reactions of the heart. In: Samuelsson B, Paoletti R (eds) Leukotrienes and other lipoxygenase products (Adv Prost Thrombox Leukotr Res 9). Raven Press, New York, 215–222

    Google Scholar 

  17. Levi R, Capurro N (1973) Histamine H2-receptor antagonism and cardiac anaphylaxis. In: Wood CJ, Simkins MA (eds) International symposium on histamine H2-receptor antagonists. Smith, Kline & French Ltd, London, 175–186

    Google Scholar 

  18. Levi R, Capurro N (1975) Cardiac histamine-ouabain interaction: Potentiation by ouabain of the arrhythmogenic effects of histamine. J Pharmacol Exp Ther 192:113–119

    Google Scholar 

  19. Levi R, Capurro N, Lee C-H (1975a) Pharmacological characterization of cardiac histamine receptors: Sensitivity to H1- and H2-receptor agonists and antagonists. Eur J Pharmacol 30:328–335

    Google Scholar 

  20. Levi R, Ganellin CR, Allan G, Willens HJ (1975b) Selective impairment of atrioventricular conduction by 2-(2-pyridyl)ethylamine and 2-(2-thiazolyl)ethylamine, two histamine H1-receptor agonists. Eur J Pharmacol 34:237–240

    Google Scholar 

  21. Levi R, Guo Z-G, (1982) Roles of histamine in cardiac dysfunction. In: Tasaka K (ed) Advances in histamine research. Pergamon Press, New York (Adv Biosciences 33) pp 213–222

    Google Scholar 

  22. Levi R, Malm JR, Bowman FO, Rosen MR (1981) The arrhythmogenic actions of histamine on human atrial fibers. Circulation Res 49:545–550

    Google Scholar 

  23. Levi R, Owen DAA, Trzeciakowski J (1982b) Actions of histamine on the heart and vasculature. In: Ganellin CR, Parsons M (eds) Pharmacology of histamine receptors. J Wright & Sons, Ltd., London (in press)

    Google Scholar 

  24. Levi R, Pappano AJ (1978) Modification of the effects of histamine and norepinephrine on the sinoatrial node pacemaker by potassium and calcium. J Pharmacol Exp Ther 204:625–633

    Google Scholar 

  25. Levi R, Zavecz JH (1979) Acceleration of idioventricular rhythms by histamine in guinea pig heart. Circulation Res 44:847–855

    Google Scholar 

  26. Levi R, Zavecz JH, Lee C-H, Allan G (1979) Histamine-drug-disease interactions and cardiac function. In: Yellin TO (ed) Histamine receptors. Spectrum Publications Inc, New York, 99–113

    Google Scholar 

  27. Levi R, Zavecz JH, Ovary Z (1978) IgE-mediated cardiac hypersensitivity reactions. Int Archs All Appl Immun 57:529–534

    Google Scholar 

  28. Lorenz W, Doenicke A, Schöning B, Neugebauer E (1981) The role of histamine in adverse reactions to intravenous agents. In: Thornton JA (ed) Adverse reactions to anesthetic drugs. Elsevier/North Holland Biomedical Press, New York, 169–238

    Google Scholar 

  29. Meyer-Burgdorff C, Seidel G, Schlüter FJ (1973) Freisetzung von Histamin und Serotonin bei extrakorporaler Zirkulation. Anaesthesist 22:212–216

    Google Scholar 

  30. Meyer-Burgdorff C, Seidel G, Wolf I (1976) Histaminfreisetzung durch Narkosemittel. Anaesthesist 25:1–5

    Google Scholar 

  31. Morrison J, Killip T (1973) Serum digitalis and arrhythmia in patients undergoing cardiopulmonary bypass. Circulation 47:341–352

    Google Scholar 

  32. Moss J, Fahmy N, Sunder N, Beaven MA (1981a) Hormonal and hemodynamic profile of an anaphylactic reaction in man. Circulation 63:210–213

    Google Scholar 

  33. Moss J, Rosow CE, Savarese JJ, Philbin DM, Kniffen KJ (1981b) Role of histamine in the hypotensive action of d-tubocurarine in man. Anaesthesiology 55:19–25

    Google Scholar 

  34. Pappano AJ (1970) Calcium-dependent action potentials produced by catecholamines in guinea pig atrial muscle fibers depolarized by potassium. Circulation Res 27:379–390

    Google Scholar 

  35. Philbin DM, Moss J, Akins CW, Rosow CE, Kono K, Schneider RC, VerLee TR, Savarese JJ (1981) The use of H1- and H2-histamine blockers with high dose morphine anesthesia: A double blind study. Anesthesiology 55:292–296

    Google Scholar 

  36. Porter J, Jick H (1977) Drug-related deaths among medical impatients. J Amer Med Assoc 237:879–881

    Google Scholar 

  37. Rockoff SD, Aker UT (1972) Contrast media as histamine liberators: VI. Arterial plasma histamine and hemodynamic responses following angiocardiography in man with 75% hypaque. Invest Radiol 7:403–406

    Google Scholar 

  38. Rose MR, Glassman E, Spencer FC (1975) Arrhythmias following cardiac surgery: relation to serum digoxin levels. Amer Heart J 89:288–294

    Google Scholar 

  39. Rosen MR, Reder RF (1981) Does triggered activity have a role in the genesis of cardiac arrhythmias? Ann Int Med 94:794–801

    Google Scholar 

  40. Rosow CE, Moss J, Philbin DM, Savarese JJ (1982) Histamine release during morphine and fentanyl anesthesia. Anesthesiology 56:93–96

    Google Scholar 

  41. Rüegg M, Jaques R (1977) Histamine-releasing effect of a corticotrophin derivative. Pharmacology 15:134–142

    Google Scholar 

  42. Senges J, Randolf U, Katus H (1977) Ventricular arrhythmias in cardiac anaphylaxis. N-S Arch Pharmakol 300:115–121

    Google Scholar 

  43. Smith PL, Kagey-Sobotka A, Bleecker ER, Traystman R, Kaplan AP, Gralnick H, Valentine MD, Permutt S, Lichtenstein LM (1980) Physiological manifestations of human anaphylaxis. J Clin Invest 66:1072–1080

    Google Scholar 

  44. Stanworth D (1980) Oligopeptide-induced release of histamine. In: Dukor P, Kallos P, Schlumberger HD, West GB (eds) Pseudo-allergic reactions. Involvement of drugs and chemicals, Vol 1: Genetic aspects and anaphylactoid reactions. Karger, Basel, pp 56–107

    Google Scholar 

  45. Trzeciakowski JP, Levi R (1981a) Cardiac histamine: A mediator in search of a function. Trends Pharmacol Sci 2:14–17

    Google Scholar 

  46. Trzeciakowski JP, Levi R (1981b) Analysis of receptors mediating histamine-induced decrease in ventricular fibrillation threshold in the guinea pig heart. Fed Proc 40:692

    Google Scholar 

  47. Vugman I, Rocha e Silva M (1966) Biological determination of histamine in living tissues and body fluids. In: Rocha e Silva M (ed) Histamine. Springer, New York (Handbook of Experimental Pharmacology, Vol 18, part 1) 81–115

    Google Scholar 

  48. Watanabe AM, Besch HR (1974) Cyclic adenosine monophosphate modulation of slow calcium influx channels in guinea pig hearts. Circulation Res 35:316–324

    Google Scholar 

  49. Wit AL, Fenoglio JJ Jr, Wagner BM, Bassett AL (1973) Electrophysiological properties of cardiac muscle in the anterior mitral valve leaflet and the adjacent atrium in the dog: Possible implication for the genesis of atrial dysrhythmias. Circulation Res 32:731–745

    Google Scholar 

  50. Wit AL, Rosen MR, Hoffman BF (1974) Electrophysiology and pharmacology of cardiac arrhythmias. II. Relationship of normal and abnormal electrical activity of cardiac fibres to the genesis of arrhythmias. B. Rentry. J Amer Heart Assoc 88:664–670

    Google Scholar 

  51. Zavecz JH, Levi R (1976) Histamine-digitalis interaction: Modification by histamine H1- and H2-receptor antagonists. Pharmacologist 18:168

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Cornell University Medical College, 1300 York Avenue, 10021, New York, NY, USA

    Roberto Levi MD, Aida A. Chenouda, Jerome P. Trzeciakowski, Zhao-Gui Guo, Laura M. Aaronson, Roger D. Luskind & Chi-Ho Lee

  2. Division of Cardiothoracic Surgery, The New York Hospital-Cornell Medical Center, New York, NY, USA

    William A. Gay, Valavanur A. Subramanian, John C. McCabe & John C. Alexander

Authors
  1. Roberto Levi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aida A. Chenouda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jerome P. Trzeciakowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhao-Gui Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laura M. Aaronson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Roger D. Luskind
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chi-Ho Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. William A. Gay
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Valavanur A. Subramanian
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. John C. McCabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. John C. Alexander
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by U.S. Public Health Service Grants GM 20091, RGP 50 GM 26145 and HL 18828

Research Fellow of the New York Heart Association, Inc

Visiting Associate Professor of Pharmacology from Hunan Medical College, People's Republic of China, supported by the China Medical Board of New York, Inc

Post-Doctoral Research Fellow supported by 1F32 HL 05536

Rights and permissions

Reprints and permissions

About this article

Cite this article

Levi, R., Chenouda, A.A., Trzeciakowski, J.P. et al. Dysrhythmias caused by histamine release in guinea pig and human hearts. Klin Wochenschr 60, 965–971 (1982). https://doi.org/10.1007/BF01716956

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01716956

Key words

Schlüsselwörter

Search

Navigation