Cardioprotective Role of Colchicine Against Inflammatory Injury in a Rat Model of Acute Myocardial Infarction

J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):446-455. doi: 10.1177/1074248418763611. Epub 2018 Apr 15.


Background: Inflammation plays a crucial role in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. A clinical trial has recently reported a smaller infarct size in a cohort of patients with ST-segment elevation myocardial infarction (MI) treated with a short colchicine course. The mechanism underlying colchicine-induced cardioprotection in the early MI phase remains unclear. We hypothesized that a short pretreatment with colchicine could induce acute beneficial effects by protecting the heart against inflammation in myocardial I/R injury.

Methods and results: Rats were subjected to 40-minute left anterior descending coronary occlusion, followed by 120-minute reperfusion. Colchicine (0.3 mg/kg) or a vehicle was administered per os 24 hours and immediately before surgery. Infarct size was significantly reduced in the colchicine group (35.6% ± 3.0% vs 46.6% ± 3.3%, P < .05). The beneficial effects of colchicine were associated with an increased systemic interleukin-10 (IL-10) level and decreased cardiac transforming growth factor-β level. Interleukin-1β was found to increase in a "time of reperfusion"-dependent manner. Colchicine inhibited messenger RNA expression of caspase-1 and pro-IL-18. Interleukin-1β injected 10 minutes prior to myocardial ischemia induced greater infarct size (58.0% ± 2.0%, P < .05) as compared to the vehicle. Colchicine combined to IL-1β injection significantly decreased infarct size (47.1% ± 2.2%, P < .05) as compared to IL-1β alone, while colchicine alone exhibited a significantly more marked cardioprotective effect than the colchicine-IL-1β association.

Conclusion: The cardioprotection induced by a short colchicine pretreatment was associated with an anti-inflammatory effect in the early reperfusion phase in our rat MI model.

Keywords: IL-1β; NLRP3 inflammasome; cardioprotection; colchicine; inflammatory injury; ischemia–reperfusion.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Caspase 1 / metabolism
  • Colchicine / pharmacology*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Inflammasomes / drug effects
  • Inflammasomes / metabolism
  • Interleukin-10 / blood
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology
  • Male
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • NLR Family, Pyrin Domain-Containing 3 Protein / drug effects
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Rats, Wistar
  • Time Factors
  • Transforming Growth Factor beta1 / metabolism


  • Anti-Inflammatory Agents
  • IL1B protein, rat
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Interleukin-10
  • Caspase 1
  • Colchicine