What is the clinical evidence from this study?

Study design: Other. Population: Coronary microembolization-induced myocardial injury (n=40). Intervention: Colchicine vs. Sham, CME alone, and CME + Colchicine + Compound C. Primary outcome: Cardiac function (LVEF, LVFS, LVEDd, LVESd) and myocardial injury markers (p=<0.05).

January 3, 2024Open Access

Colchicine ameliorates myocardial injury induced by coronary microembolization through suppressing pyroptosis via the AMPK/SIRT1/NLRP3 signaling pathway

Q: What are the key findings of this study?

Colchicine pretreatment improved coronary microembolization-induced cardiac dysfunction and reduced myocardial injury by inhibiting cardiomyocyte pyroptosis via the AMPK/SIRT1/NLRP3 signaling pathway.

Q: What does this research mean for the field?

Colchicine pretreatment improves coronary microembolization-induced cardiac dysfunction and reduces myocardial injury by inhibiting cardiomyocyte pyroptosis via the AMPK/SIRT1/NLRP3 signaling pathway. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

HLHongqing LiGuangxi Medical University HYHuafeng YangFirst Affiliated Hospital of GuangXi Medical University ZQZhenbai QinCapital Medical University

Key Result

Colchicine pretreatment improved coronary microembolization-induced cardiac dysfunction and reduced myocardial injury by inhibiting cardiomyocyte pyroptosis via the AMPK/SIRT1/NLRP3 signaling pathway.

Structured PICO

Does colchicine improve myocardial injury and cardiac dysfunction in a rat model of coronary microembolization?

Population

40 male Sprague-Dawley (SD) rats (weight 250-300 g, 8 weeks old) subjected to a coronary microembolization (CME) model via left ventricular injection of microspheres.

Intervention

Colchicine 0.3 mg/kg by gavage seven days before and on the day of modeling.

Comparator

Sham operation (saline infusion) and CME without colchicine.

Outcome

Cardiac function (LVEF, LVFS, LVEDd, LVESd) at 9 hours post-modeling, serum myocardial injury markers (LDH, cTnT, CK-MB), and pyroptosis-related indicators.surrogate

Colchicine pretreatment ameliorates coronary microembolization-induced myocardial injury and cardiac dysfunction in rats by suppressing pyroptosis via the AMPK/SIRT1/NLRP3 signaling pathway.

Main Result

p-value: p=<0.05

Limitations

The CME model constructed using polyethylene microspheres cannot fully simulate the pathophysiological changes of CME due to atheromatous plaque rupture in the real world.
The study evaluated the protective effect of colchicine pretreatment only in the acute phase of CME, while middle and long-term therapeutic effects remain unknown.
No in vitro simulation experiments were completed using a primary cardiomyocyte model.

Abstract

BACKGROUND: Coronary microembolization(CME)is a common complication in acute coronary syndrome and percutaneous coronary intervention, which is closely related to poor prognosis. Pyroptosis, as an inflammatory programmed cell death, has been found to be associated with CME-induced myocardial injury. Colchicine (COL) has potential benefits in coronary artery disease due to its anti-inflammatory effect. However, the role of colchicine in pyroptosis-related CME-induced cardiomyocyte injury is unclear. This study was carried out to explore the effects and mechanisms of colchicine on myocardial pyroptosis induced by CME. METHODS: The CME animal model was constructed by injecting microspheres into the left ventricle with Sprague-Dawley rats, and colchicine (0.3 mg/kg) pretreatment seven days before and on the day of modeling or compound C(CC)co-treatment was given half an hour before modeling. The study was divided into 4 groups: Sham group, CME group, CME + COL group, and CME + COL + CC group (10 rats for each group). Cardiac function, serum myocardial injury markers, myocardial histopathology, and pyroptosis-related indicators were used to evaluate the effects of colchicine. RESULTS: Colchicine pretreatment improved cardiac dysfunction and reduced myocardial injury induced by CME. The main manifestations were the improvement of left ventricular systolic function, the decrease of microinfarction area, and the decrease of mRNA and protein indexes related to pyroptosis. Mechanistically, colchicine increased the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK), promoted the expression of silent information regulation T1 (SIRT1), and inhibited the expression of NOD-like receptor pyrin containing 3 (NLRP3) to reduce myocardial pyroptosis. However, after CC co-treatment with COL, the effect of colchicine was partially reversed. CONCLUSION: Colchicine improves CME-induced cardiac dysfunction and myocardial injury by inhibiting cardiomyocyte pyroptosis through the AMPK/SIRT1/NLRP3 signaling pathway.

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