Impact of SGLT2i on Cardiac Remodeling and the Soleus Muscle of Infarcted Rats.

Skeletal muscle changes occur in heart failure (HF). Despite the cardioprotective effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors in HF, their impact on skeletal muscle remains poorly understood. We investigated the effects of the SGLT2 inhibitor empagliflozin (EMPA) on cardiac remodeling and the soleus muscle of rats with myocardial infarction (MI)-induced HF. METHODS: One week after MI induction, rats were assigned to Sham, Sham + EMPA, MI, and MI + EMPA groups. EMPA was administered (5 mg/kg/day) for 12 weeks. RESULTS: MI + EMPA and MI had dilated left cardiac chambers; the left atrium diameter and left ventricle end-diastolic area were smaller in MI + EMPA than MI. The ejection fraction did not differ between infarcted groups. MI + EMPA had a larger soleus cross-sectional area and higher Type II myosin heavy chain expression than MI. Carbonylated protein and malondialdehyde levels were lower and superoxide dismutase activity higher in MI + EMPA than MI. Respiratory Complex I expression was higher in MI + EMPA than MI. Metabolic enzyme activities, altered in MI, were normalized in MI + EMPA. EMPA up-regulated anabolic proteins and down-regulated catabolic proteins. CONCLUSION: Empagliflozin attenuates infarction-induced cardiac remodeling in rats. In soleus muscle, empagliflozin preserves cell trophism, reduces oxidative stress, normalizes muscle and mitochondrial metabolism, and positively modulates proteins involved in synthesis and degradation-related pathways.