Beneficial effects of the SGLT2 inhibition on oxidative skeletal muscle in infarcted rats

Abstract Introduction Metabolic, morphological, and biochemical changes in skeletal muscle are common in chronic heart failure patients. Despite the cardioprotective effects of sodium-glucose co-transporter 2 (SGLT2) inhibition in heart failure, the impact of this drug on skeletal muscle remains poorly understood. This study investigated the effects of SGLT2 inhibitor empagliflozin (EMPA) on the soleus muscle of rats with myocardial infarction (MI)-induced heart failure. Methods One week after MI induction, male Wistar rats were divided into Sham (n=10), Sham+EMPA (n=12), MI (n=10) and MI+EMPA (n=09) groups. EMPA was added to rat chow (5 mg/kg/day) for 12 weeks. Cardiac remodeling was evaluated by echocardiogram. Enzymatic activity and oxidative stress marker concentrations were assessed by spectrophotometry; protein expression was evaluated by Western blotting. After histological analysis of the left ventricle (LV), only rats with MI greater than 35% of total LV area were included in the study. Statistical analysis: ANOVA and Tukey or Kruskal–Wallis and Dunn and t test; p<0.05. Results Infarction size did not differ between groups. Infarcted groups had larger LV systolic and diastolic diameters, LV diastolic area (Sham 47±7.1; Sham+EMPA 48±4.5; MI 100±16.1*; MI+EMPA 85±10.1#† mm2; p<0.05: * vs Sham; # vs Sham+EMPA; † vs MI), and left atrial diameter (Sham 5.62±0.2; Sham+EMPA 5.65±0.3; MI 7.69±1.3*; MI+EMPA 6.85±0.9#† mm; p<0.05: * vs Sham; # vs Sham+EMPA; † vs MI); and lower LV posterior wall shortening velocity and ejection fraction than control groups. Echocardiographic changes were attenuated in MI+EMPA compared to MI. Other results are shown in Picture 1. Conclusion SGLT2 inhibitor empagliflozin attenuates infarction-induced cardiac remodeling in rats. Empagliflozin prevents increase in oxidative stress, modulates protein turnover by IGF-1 pathway, and attenuates morphological and biochemical changes in the soleus muscle of infarcted rats.