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Updated: Mar 20, 2026
Transesophageal Atrial Burst Pacing for Atrial Fibrillation Induction in Rats
Published on: February 14, 2022
Ranolazine improves oxidative stress and mitochondrial function in the atrium of acetylcholine-CaCl2 induced atrial
Deling Zou1, Ning Geng1, Yanli Chen1
1Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
Aims:
Ranolazine, an antianginal agent used for chronic stable angina treatment, was demonstrated to be effective in atrial fibrillation (AF) treatment. The aim of this study was to explore the molecular mechanisms of its anti-AF effects.
Main Methods:
AF rat model was established using acetylcholine (ACh)-CaCl2 injection for 7days followed by ACh infusion into the heart. Prior to ACh infusion, ranolazine at 10.7mg/kg/0.5ml was injected into vein and followed by 0.56mg/kg/min infusion. Blood pressure and electrocardiogram were monitored during the infusion. Histological changes of atrial tissue were observed after H&E staining. Activities and protein expression of NADPH oxidase-4, xanthine oxidase, glutathione peroxidase and superoxide dismutase were examined using commercial assay kits and Western botting, respectively. Mitochondrial functions were evaluated through membrane potential, ATP production, activities of complex I and III and reactive oxygen species production. Apoptosis was measured using TUNEL staining. Protein expression of apoptotic proteins Bcl-2, Bax and cleaved-caspase 3 and Akt/mTOR signaling proteins were detected using Western blotting.
Key Findings:
Results demonstrated that ranolazine attenuated AF in ACh-CaCl2-exposed rats. In addition, ranolazine restored mitochondrial function, suppressed oxidative stress, and inhibited atrial cells apoptosis. Furthermore, the activated Akt/mTOR signaling pathway induced by AF was further activated by ranolazine.
Significance:
The present study confirms the effects of ranolazine on AF rats induced by ACh-CaCl2, and provides evidence that the anti-AF effects are associated with the restoration of mitochondrial function and activation of the Akt/mTOR signaling pathway in atrial tissue.
Insights
Ranolazine effectively treats atrial fibrillation (AF) by restoring mitochondrial function and activating the Akt/mTOR pathway in rats. This study reveals ranolazine
Area of Science:
- Cardiovascular Research
- Molecular Cardiology
- Pharmacology
Background:
- Ranolazine, primarily an antianginal drug, shows efficacy in treating atrial fibrillation (AF).
- Understanding the molecular mechanisms behind ranolazine's anti-AF effects is crucial for therapeutic development.
Purpose of the Study:
- To investigate the molecular mechanisms underlying ranolazine's effectiveness in treating atrial fibrillation.
- To explore ranolazine's impact on oxidative stress, mitochondrial function, and apoptosis in an AF rat model.
Main Methods:
- An atrial fibrillation rat model was induced using acetylcholine and calcium chloride.
- Ranolazine's effects were assessed by monitoring hemodynamic and electrocardiographic parameters.
- Atrial tissue analysis included histological examination, oxidative stress marker assessment, mitochondrial function assays, and apoptosis evaluation via TUNEL and Western blotting.
Main Results:
- Ranolazine significantly attenuated atrial fibrillation in the rat model.
- The drug restored mitochondrial function, reduced oxidative stress, and inhibited apoptosis in atrial cells.
- Ranolazine further activated the Akt/mTOR signaling pathway, which was initially upregulated by AF.
Conclusions:
- Ranolazine demonstrates anti-atrial fibrillation effects in a rat model induced by acetylcholine and calcium chloride.
- These effects are linked to the restoration of mitochondrial function and the activation of the Akt/mTOR signaling pathway in atrial tissue.
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