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Updated: Aug 5, 2025
Acute Myocardial Infarction in Rats
Published on: February 16, 2011
Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction
Mark B Plotnikov1,2, Galina A Chernysheva1, Vera I Smol'yakova1
1Department of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, 634028 Tomsk, Russia.
Abstract:
Activation of c-Jun N-terminal kinases (JNKs) is involved in myocardial injury, left ventricular remodeling (LV), and heart failure (HF) after myocardial infarction (MI). The aim of this research was to evaluate the effects of a selective JNK inhibitor, 11H-indeno [1,2-b]quinoxalin-11-one oxime (IQ-1), on myocardial injury and acute myocardial ischemia/reperfusion (I/R) in adult male Wistar rats. Intraperitoneal administration of IQ-1 (25 mg/kg daily for 5 days) resulted in a significant decrease in myocardial infarct size on day 5 after MI. On day 60 after MI, a significant (2.6-fold) decrease in LV scar size, a 2.2-fold decrease in the size of the LV cavity, a 2.9-fold decrease in the area of mature connective tissue, and a 1.7-fold decrease in connective tissue in the interventricular septum were observed compared with the control group. The improved contractile function of the heart resulted in a significant (33%) increase in stroke size, a 40% increase in cardiac output, a 12% increase in LV systolic pressure, a 28% increase in the LV maximum rate of pressure rise, a 45% increase in the LV maximum rate of pressure drop, a 29% increase in the contractility index, a 14% increase in aortic pressure, a 2.7-fold decrease in LV end-diastolic pressure, and a 4.2-fold decrease in LV minimum pressure. We conclude that IQ-1 has cardioprotective activity and reduces the severity of HF after MI.
Insights
A selective c-Jun N-terminal kinase (JNK) inhibitor, IQ-1, demonstrated significant cardioprotective effects in rats. This JNK inhibitor reduced myocardial injury, improved cardiac function, and mitigated heart failure after myocardial infarction.
Area of Science:
- Cardiovascular Biology
- Pharmacology
- Molecular Medicine
Background:
- c-Jun N-terminal kinases (JNKs) play a crucial role in myocardial injury, left ventricular remodeling, and heart failure following myocardial infarction (MI).
- Selective inhibition of JNK pathways presents a potential therapeutic strategy for mitigating cardiac damage and dysfunction.
Purpose of the Study:
- To investigate the cardioprotective effects of a novel selective JNK inhibitor, 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1).
- To evaluate the impact of IQ-1 on myocardial injury, infarct size, and cardiac remodeling in a rat model of myocardial infarction and ischemia/reperfusion.
Main Methods:
- Adult male Wistar rats were administered IQ-1 intraperitoneally (25 mg/kg daily for 5 days) following induced myocardial infarction.
- Assessment of myocardial infarct size, left ventricular (LV) scar size, LV cavity dimensions, and connective tissue area was performed.
- Cardiac contractile function was evaluated by measuring stroke size, cardiac output, LV pressures, and pressure changes.
Main Results:
- IQ-1 significantly reduced myocardial infarct size by day 5 post-MI.
- Long-term administration of IQ-1 led to substantial reductions in LV scar size, LV cavity dimensions, and fibrotic tissue formation.
- Significant improvements in cardiac function were observed, including increased stroke size, cardiac output, LV systolic pressure, and contractility, alongside reduced LV end-diastolic pressure.
Conclusions:
- The selective JNK inhibitor IQ-1 exhibits significant cardioprotective activity.
- IQ-1 effectively reduces myocardial injury, cardiac remodeling, and the severity of heart failure after myocardial infarction in a rat model.
- Targeting JNK pathways with inhibitors like IQ-1 holds promise for treating post-MI cardiac complications.
