Skip to main content
Log in

Cardiotoxicity of colchicine in the rat

  • Originals
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Objectives

Colchicine poisoning may be lethal and a decrease in cardiac function has been reported in several case reports, but the precise cardiotoxicity of colchicine remains unknown.

Design

The experimental in vitro study assessed the intrinsic contractility of left ventricular papillary muscle in rats, 24 h after administration of intraperitoneal colchicine or saline.

Results

The administration of colchicine (2 or 4 mg·kg−1) in adult Wistar rats markedly impaired intrinsic myocardial contractility, as shown by a decrease in maximum shortening velocity (−32 and −61%, respectively), active isometric force (−47 and −65%, respectively), and peak power output (−57 and −69%, respectively) of left ventricular papillary muscle. Colchicine impaired isotonic relaxation and load dependence of relaxation, suggesting a decrease in sarcoplasmic reticulum function. Conversely, colchicine significantly accelerated isometric relaxation, suggesting a decrease in calcium myofilament sensitivity. Myothermal economy was markedly impaired only in some rats (3/10 in each group), in which the negative inotropic effect of colchicine appeared to be more particularly pronounced.

Conclusion

The results indicate that the administration of high doses of colchicine induced intrinsic cardiotoxic effects. Due to its amplitude, such cardiotoxic action may participate in the fatal outcome of acute colchicine poisoning.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Kaplan MM, Alling DW, Zimmerman HJ, Wolfe JH, Sepersky RA, Hirsch GS, Elta GH, Glick KA, Eagen KA (1986) A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med 315:1448–1454

    Google Scholar 

  2. Zemer D, Pras M, Sohar E, Modan M, Cabili S, Gafni J (1986) Colchicine in the prevention and treatment of the amyloidosis of familial mediterranean fever. N Engl J Med 314:1001–1005

    Google Scholar 

  3. Guindo J, de la Serna R, Ramio J, de Miguel Diaz MA, Subirana MT, Perez Ayuso MJ, Cosin J, Bayés de Luna A (1990) Recurrent pericarditis. Relief with colchicine. Circulation 82:1117–1120

    Google Scholar 

  4. Taylor EW (1965) The mechanism of colchicine inhibition of mitosis. I. Kinetics of inhibition and the binding of3H-colchicine. J Cell Biol 25:145–160

    Google Scholar 

  5. Bismuth C, Gaultier M, Conso F (1977) Aplasie médullaire après intoxication aiguë à la colchicine: 20 cas. Nouv Presse Méd 6:1625–1629

    Google Scholar 

  6. Bismuth C, Sebag S (1981) Choc cardiogénique lors d'une intoxication aiguë par la colchicine. Nouv Presse Méd 10:1073

    Google Scholar 

  7. Charbonneau P, Troussard X, Grollier G, Commeau P, Potier JC, Bazin C (1985) Apport de l'échocardiographie et de la scintigraphie cardiaque dans l'intoxication aiguë par la colchicine: mise en évidence d'un effect inotrope négatif. Réanim Soins Intens Méd Urg 1:69 (Abstract)

    Google Scholar 

  8. Lecarpentier Y, Martin JL, Gastineau P, Hatt PY (1982) Load dependence of mammalian heart relaxation during cardiac hypertrophy and heart failure. Am J Physiol 24:H855-H861

    Google Scholar 

  9. Riou B, Lecarpentier Y, Chemla D, Viars P (1990) In vitro effects of etomidate on intrinsic myocardial contractility in the rat. Anesthesiology 72:330–340

    Google Scholar 

  10. Brutsaert DL, Claes VA (1974) Onset of mechanical activation of mammalian heart muscle in calcium- and strontium-containing solutions. Circ Res 35:345–357

    Google Scholar 

  11. Chemla D, Lecarpentier Y, Martin JL, Clergue M, Antonetti A, Hatt PY (1986) Relationship between inotropy and relaxation in rat myocardium. Am J Physiol 250:H1008-H1016

    Google Scholar 

  12. Lecarpentier YC, Martin JL, Claes V, Chambaret JP, Migus A, Antonetti A, Hatt PY (1985) Real-time kinetics of sarcomere relaxation by laser diffraction. Circ Res 56:331–339

    Google Scholar 

  13. Housmans PR, Lee NKM; Blinks JR (1983) Active shortening retards the decline of intracellular calcium transient in mammalian heart muscle. Science 251:159–161

    Google Scholar 

  14. Lecarpentier Y, Bugaisky LB, Chemla D, Mercadier JJ, Schwartz K, Whalen RG, Martin JL (1987) Coordinated changes in contractility, energetics, and isomyosins after aortic stenosis. Am J Physiol 252:H275-H282

    Google Scholar 

  15. Hill AV (1938) The heat of shortening and the dynamic constants of muscle. Proc R Soc Biol [Lond] 126:136–195

    Google Scholar 

  16. Woledge RC, Curtin NA, Homsher E (1985) Energetic aspects of muscle contraction. Monogr Physiol Soc 41:27–117

    Google Scholar 

  17. Clergue M, Riou B, Lecarpentier Y (1990) Inotropic and lusitropic effects of chlorpromazine on rat left ventricular papillary muscle. J Pharmacol Exp Ther 253:296–304

    Google Scholar 

  18. Vittone L, Grassi A, Chiappe L, Argel M, Cingolani HE (1981) Relaxing effect of pharmacologic interventions increasing cAMP in rat heart. Am J Physiol 240:H441-H447

    Google Scholar 

  19. Sys SU Housmans PR, Van Ocken ER, Brutsaert DL (1984) Mechanisms of hypoxia-induced decrease of load-dependence of relaxation in cat papillary muscle. Pflügers Arch 401:368–373

    Google Scholar 

  20. Riou B, Baud FJ, Astier A, Barriot P, Lecarpentier Y (1990) In vitro demonstration of the antidotal efficacy of hydroxocobalamin in cyanide poisoning. J Neurosurg Anesthesiol 2:296–304

    Google Scholar 

  21. Paradise NF, Schmitter JL, Surmitis JM (1981) Criteria for adequate oxygenation of isometric kitten papillary muscle. Am J Physiol 241:H348-H353

    Google Scholar 

  22. Rappaport L, Samuel JL (1988) Microtubules in cardiac myocytes. Int Rev Cytol 113:101–143

    Google Scholar 

  23. Terrien N, Urtizberea M, Scherrmann JM (1988) Immunotoxicotherapy for colchicine poisoning: toxicological and pharmacological features of an experimental model simulating human poisoning. Arch Toxicol [Suppl 12]:322–325

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mery, P., Riou, B., Chemia, D. et al. Cardiotoxicity of colchicine in the rat. Intensive Care Med 20, 119–123 (1994). https://doi.org/10.1007/BF01707666

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01707666

Key words

Navigation