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Updated: Jun 6, 2025
An Experimental Model of Diet-Induced Metabolic Syndrome in Rabbit: Methodological Considerations, Development, and Assessment
Published on: April 20, 2018
Empagliflozin Ameliorates Atrial and Ventricular Remodeling and Arrhythmogenesis in an Overweight Rabbit Model
Wen-Han Cheng1,2,3, Li-Wei Lo2,3, Yu-Hui Chou2,3
1Division of Cardiology, Department of Internal Medicine, National Yang Ming Chiao Tung University Hospital, Yilan.
Background:
Overweight is associated with dysrhythmia and sudden cardiac death, while sodium glucose co-transporter-2 inhibitors (SGLT2-is) have been shown to possess cardioprotective effects in patients with hyperglycemia.
Objectives:
The aim of this study was to investigate the impact of overweight on cardiac remodeling and the potential effect of SGLT2-is.
Methods:
Twenty-four rabbits were randomized into 4 groups: controls (Group 1), high-fat diet (HFD) (Group 2), controls treated with empagliflozin (Group 3), and HFD treated with empagliflozin (Group 4). All rabbits underwent electrophysiologic studies and ventricular tachycardia/ventricular fibrillation (VF) inducibility tests (maximal output with shortest 1:1 cycle length pacing). Atrial and ventricular myocardium were harvested for Western blot and Trichrome staining.
Results:
Among all groups, Group 2 had the longest atrial effective refractory periods (ERPs) in both left and right atria, as well as the longest ventricular ERPs in both left and right ventricles. VF inducibility was highest in Group 2. The degree of fibrosis in both atria and ventricles was most severe in Group 2 and similar to that in Group 4. Enhanced calcium handling protein (CaV 1.2) expressions were noted in Group 2 compared to those in Group 1 and Group 3, respectively, and returned to baseline in Group 4.
Conclusions:
Overweight causes atrial and ventricular remodeling with prolongation of effective refractoriness, increased vulnerability to VF induction, upregulation of calcium handling proteins, and advanced fibrosis. Empagliflozin attenuates these remodeling effects, leading to decreased cardiac arrhythmogenicity and a reduced risk of sudden cardiac death.
Insights
Overweight worsens cardiac remodeling and increases sudden cardiac death risk. Sodium glucose co-transporter-2 inhibitors (SGLT2-is) like empagliflozin mitigate these negative effects, reducing cardiac arrhythmogenicity.
Area of Science:
- Cardiology
- Metabolic Disorders
- Pharmacology
Background:
- Overweight is linked to cardiac arrhythmias and sudden cardiac death.
- Sodium glucose co-transporter-2 inhibitors (SGLT2-is) demonstrate cardioprotective properties, particularly in hyperglycemic individuals.
Purpose of the Study:
- To evaluate the impact of overweight on cardiac remodeling.
- To investigate the potential cardioprotective effects of SGLT2-is in the context of overweight.
Main Methods:
- A rabbit model was used, with groups including controls, high-fat diet (HFD), controls with empagliflozin, and HFD with empagliflozin.
- Electrophysiologic studies and ventricular tachycardia/fibrillation (VF) inducibility tests were performed.
- Cardiac tissue was analyzed for fibrosis and calcium handling protein expression.
Main Results:
- High-fat diet (overweight model) led to prolonged effective refractory periods and increased VF inducibility.
- Significant fibrosis was observed in overweight rabbits, with empagliflozin showing partial attenuation.
- Calcium handling protein expression was upregulated in the overweight group, returning to baseline with empagliflozin treatment.
Conclusions:
- Overweight induces cardiac remodeling, including prolonged refractoriness, increased VF vulnerability, and fibrosis.
- Empagliflozin effectively attenuates these adverse remodeling effects, reducing cardiac arrhythmogenicity and the risk of sudden cardiac death.
