Abstract Introduction Although a sodium-glucose co-transporter 2 inhibitor (SGLT2i) is approved for the treatment of both heart failure with reduced and preserved ejection fraction, its direct cardioprotective effects remain unknown (1-3). If the effect is demonstrated, the use of SGLT2i can be considered for heart failure in patients with severe renal impairment, including those on dialysis. Purpose This study aims to demonstrate the direct cardioprotective effects of SGLT2is in nephrectomized rats after ischemia-reperfusion (I/R) injury (RKIR model) and nephrectomized rats without I/R (RK-control model). Methods We used 8-week-old male Sprague-Dawley rats. Under general anesthesia, all rats underwent bilateral nephrectomy before randomization. We randomly assigned them into vehicle (dimethyl sulfoxide; DMSO, n = 15) or SGLT2i (empagliflozin, 10 mg/kg iv, n = 17) treated groups. Additionally, in the RKIR model, we induced ischemia-reperfusion (IR) injury by left anterior descending (LAD) artery ligation for 30 minutes, followed by reperfusion for 8 vehicle-treated and 9 empagliflozin-treated rats. Twenty-four hours after recovery, we assessed general condition with modified mouse clinical score, hemodynamics and left ventricular (LV) function among four groups with/without IR: vehicle-treated IR (IR, n = 8), and empagliflozin-treated IR (E-IR, n = 9) in the RKIR model and vehicle-treated without IR (Control, n = 7), empagliflozin-treated without IR (Empa, n = 8) in the RK-control model. Results In the RKIR model (Figure 1), empagliflozin significantly improved general condition. Empagliflozin significantly increased mean arterial pressure (87.4 ± 9.3 mmHg vs. 74.0 ± 10.4 mmHg, p 0.05) and lowered LV end-diastolic pressure (LVEDP) (15.1 ± 5.6 mmHg vs. 25.0 ± 6.0 mmHg, p 0.01) and right atrial pressure (2.5 ± 0.7 mmHg vs. 5.2 ± 2.2 mmHg, p 0.01), accompanied by augmented LV max +dP/dt (5659 ± 899 mmHg/s vs. 4330 ± 1221 mmHg/s, p 0.05). In the RK-Control model, empagliflozin treatment improved general conditions, while did not change hemodynamic parameters (Figure 2). Conclusion Empagliflozin preserves hemodynamics and LV function in nephrectomized rats after ischemia-reperfusion injury. Our data suggests a potential therapeutic benefit of SGLT2is in heart failure patients who cannot fully benefit from the kidney-mediated effects.Figure 1 Figure 2
Akiyoshi et al. (Sat,) studied this question.