Empagliflozin attenuates post-injury myocardial remodeling in a rat isoproterenol model: a morphological and morphometric study

Adverse post-myocardial infarction remodeling is a key pathway toward chronic heart failure. While sodium-glucose cotransporter-2 (SGLT2) inhibitors improve outcomes in heart failure, evidence on their structural effects when therapy is initiated after the acute injury phase remains limited. Study aim – to evaluate whether delayed initiation of empagliflozin attenuates histological remodeling features and reduces morphometric indices of cardiomyocyte hypertrophy in rats with isoproterenol-induced myocardial injury. Sixty male outbred white rats (200-250 g) were allocated to three groups (n=20 each): intact control, isoproterenol (ISO) + placebo, and ISO + empagliflozin. Myocardial injury was induced by ISO (85 mg/kg/day, subcutaneously, on days 0 and 1). From day 14, animals received empagliflozin (10 mg/kg/day by oral gavage) or vehicle for 30 days. Hearts were harvested on day 44. Left-ventricular sections were obtained from subendocardial, intramural, and subepicardial layers and stained with hematoxylin-eosin and Masson’s trichrome. Digital morphometry quantified cardiomyocyte and nuclear area. Statistical analysis was conducted using the IBM SPSS 26.0 software (IBM, USA). It was established that ISO caused microvascular congestion, interstitial edema, cardiomyocyte disarray, and increased collagen deposition on Masson’s staining. Delayed empagliflozin reduced the qualitative severity of injury and attenuated hypertrophic morphometry. Cardiomyocyte area was higher in ISO + placebo than in control (342.8±12.5 μm² vs 223.2±8.4 μm²; p