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.
Similar content being viewed by others
References
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
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
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
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
Bismuth C, Gaultier M, Conso F (1977) Aplasie médullaire après intoxication aiguë à la colchicine: 20 cas. Nouv Presse Méd 6:1625–1629
Bismuth C, Sebag S (1981) Choc cardiogénique lors d'une intoxication aiguë par la colchicine. Nouv Presse Méd 10:1073
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)
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
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
Brutsaert DL, Claes VA (1974) Onset of mechanical activation of mammalian heart muscle in calcium- and strontium-containing solutions. Circ Res 35:345–357
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
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
Housmans PR, Lee NKM; Blinks JR (1983) Active shortening retards the decline of intracellular calcium transient in mammalian heart muscle. Science 251:159–161
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
Hill AV (1938) The heat of shortening and the dynamic constants of muscle. Proc R Soc Biol [Lond] 126:136–195
Woledge RC, Curtin NA, Homsher E (1985) Energetic aspects of muscle contraction. Monogr Physiol Soc 41:27–117
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
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
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
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
Paradise NF, Schmitter JL, Surmitis JM (1981) Criteria for adequate oxygenation of isometric kitten papillary muscle. Am J Physiol 241:H348-H353
Rappaport L, Samuel JL (1988) Microtubules in cardiac myocytes. Int Rev Cytol 113:101–143
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
Author information
Authors and Affiliations
Rights 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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01707666