Cardiotoxicity of colchicine in the rat.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Mery
P
P
Institut National de la Santé et de la Recherche Médicale, Unité 275, LOA-ENSTA-Ecole Polytechnique, Palaiseu, France.
Riou
B
B
Chemla
D
D
Lecarpentier
Y
Y
D000208:Acute Disease; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003078:Colchicine / Q000506:poisoning*; D004353:Drug Evaluation, Preclinical; D004734:Energy Metabolism / Q000187:drug effects; D007274:Injections, Intraperitoneal; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D010210:Papillary Muscles / Q000187:drug effects; D011041:Poisoning / Q000150:complications; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D003078:Colchicine