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Ipragliflozin Prevents the Worsening of Ischemic Heart Failure in Diabetic Rats Independent of its Diuretic Effect
Author(s) -
Kamada Kazuhiro,
Saku Keita,
Kishi Takuya,
Akashi Takuya,
Takehara Takako,
Tsutsui Hiroyuki,
Sunagawa Kenji
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.687.14
Subject(s) - medicine , empagliflozin , heart failure , ejection fraction , diabetes mellitus , myocardial infarction , hemodynamics , cardiology , diuretic , endocrinology , type 2 diabetes
Although diabetes mellitus (DM) increases cardiovascular events, no clinical trials had ever shown the benefit of glucose‐lowering therapy on heart failure (HF). Recently, sodium‐glucose cotransporter 2 (SGLT2) inhibitor has shown to lower cardiovascular events and hospitalization for HF in DM (EMPA‐REG OUTCOME). To clarify the beneficial mechanisms of SGLT2‐inhibitor for HF, we investigated the impact of SGLT2‐inhibitor, ipragliflozin, on hemodynamics and cardiac function in a rat model of HF with DM. Methods We allocated Sprague‐Dawley rats into streptozotocin (60 mg/kg)‐induced DM or non‐DM groups. We created myocardial infarction (MI) in both groups and administered ipragliflozin (3 mg/kg/day) or vehicle from two weeks after MI. Four weeks after the initiation of treatment, we compared hemodynamic parameters among 4 groups (DM‐MI+ipragliflozin, n=9; DM‐MI+vehicle, n=6; MI+ipragliflozin, n=7; MI+vehicle, n=7). Results Daily urine volume nearly quadrupled in DM rats in comparison with non‐DM rats. In DM rats, ipragliflozin significantly lowered blood glucose (309±36 vs. 478±107 mg/dL, p <0.01), prevented the worsening of left ventricular (LV) ejection fraction (−1.4±4.8 vs. −8.8±5.1%, p <0.05), increased max LVdP/dt (6193±667 vs. 5015±456 mmHg/sec, p <0.01) and tended to decrease LV end‐diastolic pressure (24.8±5.3 vs. 30.5±5.7 mmHg, p =0.069). However, ipragliflozin did not affect urine volume. In non‐DM rats, the beneficial effects of ipragliflozin on HF were limited. Conclusions Ipragliflozin attenuated the worsening of HF in DM rats, while its beneficial effects were obscured in non‐DM rats. These results indicate that ipragliflozin has direct cardioprotective effects on HF in DM independent of its diuretic effects.