Influence of the SGLT2 inhibitor empagliflozin on post myocardial infarction rat hearts

Abstract Studies have shown that inhibition of the sodium glucose transporter protein 2 (SGLT2) reduces cardiovascular death in patients with heart failure and reduced ejection fraction. However, the mechanisms involved in the benefits of SGLT2 inhibitors are poorly understood. Objective To evaluate the effects of empagliflozin (EMP) on normal and post-myocardial infarction (MI) rat hearts. Methods Male Wistar rats (n=80) were assigned into four groups: Sham; Sham treated with EMP (Sham-EMP); myocardial infarction (MI); and MI treated with EMP (MI-EMP). EMP added to rat chow (5 mg/kg/day) was initiated 10 days after MI induction and maintained for 12 weeks. Echocardiogram was performed at the end of the experimental period. Markers of oxidative stress, energy metabolism, and respiratory complex activity were analyzed in left ventricular myocardium. Statistical analysis: ANOVA. Results Histological evaluation showed that EMP did not change infarct size. Cardiac structural and functional parameters did not differ between MI-EMP and MI groups. Myocardial oxidative stress, evaluated by lipid hydroperoxide concentration, was lower in MI-EMP than MI group (Sham 143±26; Sham-EMP 123±20; MI 183±29; MI-EMP 137±11 nmol/g tissue). Glutathione peroxidase was lower in the infarcted groups and did not differ between MI-EMP and MI (Sham 37.6±6.14; Sham-EMP 40.8±10.1; MI 27.7±6.61; MI-EMP 26.5±6.80 μmol/g tissue). Activity of the energy metabolism enzymes lactate dehydrogenase (Sham 45.2±6.65; Sham-EMP 41.1±9.33; MI 58.4±14.4; MI-EMP 55.7±10.1 nmol/mg protein) and citrate synthase (Sham 30.4±4.25; Sham-EMP 37.2±4.85; MI 45.8±8.47; MI-EMP 46.5±9.95 nmol/mg protein) was higher, and β-hydroxyacyl-CoA dehydrogenase (Sham 24.0±3.12; Sham-EMP 20.4±4.84; MI 16.9±4.81; MI-EMP 14.4±4.58 nmol/mg protein) lower in the infarcted groups with no differences between MI-EMP and MI. Respiratory complexes I and II, and ATP synthase did not differ between the infarcted groups. Conclusion Empagliflozin reduces myocardial oxidative stress independent of changes in antioxidant enzymes activity, energy metabolism, and respiratory complex activity in the myocardium of infarcted rats. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Fapesp, CNPq