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Table 7 Summary of the effects of SGLT-2 inhibitors on cardiac ionic homeostasis in animal models

From: Potential mechanisms responsible for cardioprotective effects of sodium–glucose co-transporter 2 inhibitors

Animal species Model Drug/dose/route Major findings Interpretation References
Rabbits and rats In vitro isolated ventricular myocytes Empagliflozin (1 μmol/l)/media/3 h ↓ Myocardial [Na+]c and [Ca2+]c
↑ Myocardial [Ca2+]m
These effects were strongly reduced after pre-treated with NHE inhibitor
Empagliflozin has cardiac effects by decreasing myocardial cytoplasmic [Na+]c and [Ca2+]c and increasing [Ca2+]m through inhibition of NHE directly [116]
ob/ob mice T2DM/obesity (LV diastolic dysfunctions) Empagliflozin (10 mg/kg/days)/PO/6 weeks ↑ SERCA2a/PLN ratio, PLN phosphorylation Empagliflozin enhances SERCA2a activity leading to improve cardiac contractile dysfunction in ob/ob mice [60]
Seipin knockout (SKO) mice Diabetic lipodystrophic cardiomyopathy Dapagliflozin (1 mg/kg/days)/PO/8 weeks ↑ SERCA2a/PLN ratio Dapagliflozin enhances SERCA2a activity leading to improve cardiac contractile dysfunction in SKO mice [69]
  1. [Na+]c cytoplasmic Na+ concentration, [Ca2+]c cytoplasmic Ca2+ concentration, [Ca2+]m mitochondrial Ca2+ concentration, NHE Na+/H+ exchange, T2DM type 2 diabetic mellitus, LV left ventricular, PO per oral, SERCA2a sarcoplasmic endoplasmic reticulum calcium (Ca2+) ATPase, PLN phospholamban