Table 3 Summary of the effects of SGLT-2 inhibitors on cardiovascular function in animal models
Animal species | Model | Drug/dose/route | Major findings | Interpretation | References |
|---|---|---|---|---|---|
Wistar rats | Streptozotocin-induced diabetic cardiomyopathy | Empagliflozin (30 or 10 mg/kg/days)/PO/8 weeks | ↑ ESP, + dp/dt and − dp/dt ↓ EDP | Empagliflozin improved LV function in streptozotocin-induced diabetic cardiomyopathy rats | [62] |
SHR/NDmcr-cp (+/+) rats | Prediabetes/metabolic syndrome | 0.03% empagliflozin/diet/7 weeks | ↔ HR, SBP, DBP, locomotor activity, LF-SBP, sBRG and LF/HF ratio of PI | Empagliflozin did not have effect on heart rate, blood pressure, sympathetic activity, or baroreceptor function in genetic prediabetic metabolic syndrome rats | [57] |
db/db mice | Diabetes/obesity (diastolic dysfunction and LVH) | Empagliflozin (10 mg/kg/days)/PO/5 weeks | ↑ Septal wall motion ↓ CO, SV, LV filling pressure ↔ EF, FS | Empagliflozin improved septal wall motion and LV filling pressure in db/db mice | [59] |
db/db mice | Diabetes/obesity (diastolic dysfunction and LVH) | 0.03% empagliflozin/diet/10 weeks | ↓ Impairment of vascular endothelium-dependent relaxation in thoracic aortas | Empagliflozin attenuated vascular dilating dysfunction in db/db mice | [58] |
ob/ob mice | T2DM/obesity (LV diastolic dysfunctions) | Empagliflozin (10 mg/kg/days)/PO/6 weeks | ↓ E wave, E wave deceleration time, Tau, EDPVR ↔ HR, EF, FS and ESPVR | Empagliflozin improved LV diastolic function but not systolic function in ob/ob mice | [60] |
BTBR ob/ob mice | T2DM | Dapagliflozin (1 mg/kg/days)/PO/8 weeks | ↓ ESV, EDV, IVSs, IVSd ↑ EF, FS ↔ HR | Dapagliflozin improved LV function in BTBR ob/ob mice | [63] |
Seipin knockout (SKO) mice | Diabetic lipodystrophic cardiomyopathy | Dapagliflozin (1 mg/kg/days)/PO/8 weeks | ↑ E/A ratio and EF ↓ IVRT, DT and EDWT ↔ EDV | Dapagliflozin improved both systolic and diastolic LV function in SKO mouse | [69] |
Rats | High fat diet induced obese-insulin resistance for 4 weeks then I/R injury by LAD ligation | Dapagliflozin (1 mg/kg/days)/PO/4 weeks | Before I/R injury ↑ E/A ratio and EF ↓ HR, IVRT, DT and EDWT During I/R injury ↑ Time to 1st VT/VF onset ↓ Arrhythmia score ↑ Gap junction protein connexin 43 expression ↔ Number of VT/VF and VT/VF incidence ↑ ESP, SV, EF and SW ↓ HR, EDP, ESV and EDV | Dapagliflozin improved both systolic and diastolic LV function and heart rate variability in pre-diabetic rats Dapagliflozin prevented cardiac arrhythmia in pre-diabetic rats with cardiac I/R injury | [64] |
Wistar rats | MI by LAD ligation in rats | Dapagliflozin (0.1 mg/kg/days)/PO/Start after 1-day infarction for 4 weeks | ↑ Maximal rate of LV + dP/dt and − dP/dt | Dapagliflozin improved cardiac function during post-infarction remodeling in rats | [65] |