Effects of Empagliflozin Combined with Anaerobic, Aerobic, and Endurance Swimming Protocols on Cardiac Structure and Electrophysiology in Healthy Rats

Objective: Sodium–glucose cotransporter 2 (SGLT2) inhibitors, particularly empagliflozin, have attracted considerable attention because of their cardiovascular benefits beyond glycemic control. However, the interaction between empagliflozin and exercise-induced physiological cardiac remodeling in healthy individuals remains insufficiently understood. This study investigated the effects of different swimming exercise protocols (anaerobic, aerobic, and endurance), administered alone or in combination with empagliflozin, on cardiac structure and electrophysiology. Methods: Thirty-six male Sprague–Dawley rats were randomly assigned to six groups (n = 6 per group): anaerobic (An), aerobic (Ae), endurance (En), and the corresponding exercise groups combined with empagliflozin (An + Empa, Ae + Empa, and En + Empa). Empagliflozin was administered by oral gavage at a dose of 15 mg/kg/day for 30 days. Transthoracic echocardiography, electrocardiography (ECG), and gastrocnemius electromyography were performed at baseline and at the end of the study to assess cardiac remodeling, heart rate, and neuromuscular function. The study was carried out over a 30-day intervention period following ethics committee approval on 24 July 2024. Results: No significant between-group differences were observed in echocardiographic parameters before the intervention. On day 30, significant differences were identified among the groups in interventricular septal thickness at end-diastole (IVSd) (p = 0.027), left ventricular internal diameter at end-diastole (LVIDd) (p = 0.009), and end-diastolic volume (EDV) (p = 0.014). Bonferroni-corrected post hoc analysis showed that the aerobic exercise plus empagliflozin group differed from several exercise-only groups, particularly in parameters related to ventricular size and filling volume, including LVIDd and EDV (p < 0.008). On day 30, electrocardiographic repolarization-related parameters, including QT, QTc, JT, and Tpeak–Tend intervals, also differed significantly among the groups (all p < 0.05). In post hoc analysis, the anaerobic exercise group showed significant differences in QT and JT intervals compared with the aerobic and endurance groups (p < 0.008). In the anaerobic protocol, empagliflozin was associated with a reduction in heart rate compared with the corresponding control group (p = 0.019). No significant between-group differences were observed in EMG findings. Conclusions: Different exercise protocols induce distinct patterns of adaptation in cardiac structure and electrophysiology in healthy rats. Empagliflozin (15 mg/kg/day) may modulate exercise-induced cardiac responses in a modality-dependent manner; the most pronounced echocardiographic effects were observed in the aerobic protocol, whereas the effect on heart rate was observed in the anaerobic protocol. These findings highlight the need for longer-term and mechanistic studies to further clarify the effects of SGLT2 inhibitors on physiological cardiac remodeling.