Background
Empagliflozin (EMPA) reduces heart failure hospitalization and mortality. The benefit in terms of ventricular arrhythmia and contractility has not been explored.
Conclusions
EMPA treatment reduced ventricular arrhythmia vulnerability and mitigated contractile dysfunction in the global I/R model while improving calcium cycling and mitochondrial redox by SGLT2-independent mechanisms.
Methods
Langendorff-perfused rabbit hearts were subjected to 30 min of complete perfusion arrest and reperfusion. Either EMPA (1 μM) or normal saline (controls) was then infused into the perfusate in a randomized fashion. Ten minutes following drug infusion, calcium imaging was performed. At the end of each experiment, the heart was electrically stimulated 5 times to assess the inducibility of ventricular fibrillation (VF). In a separate series of experiments, left ventricular (LV) pressure and epicardial NADH fluorescence were simultaneously recorded. LV specimens were then collected for western blotting.
Objective
To determine the direct effects of EMPA on ventricular arrhythmia and cardiac contractility in an ex-vivo model of global ischemia-reperfusion (I/R).
Results
Post-ischemia, EMPA treatment was associated with reduction in the induction of VF >10s (rate of induction: 16.7 ± 3.3% vs. 60 ± 8.7% in control hearts, p = 0.003), improvement of LV developed pressure (LVDP; 68.10 ± 9.02% vs. 47.61 ± 5.15% in controls, p = 0.03) and reduction of NADH fluorescence (87.42 ± 2.79% vs. 112.88 ± 2.27% in control hearts, p = 0.04) along with an increase in NAD+/NADH ratio (2.75 ± 0.55 vs. 1.09 ± 0.32 in the control group, p = 0.04) A higher calcium amplitude alternans threshold was also observed with EMPA-treatment (5.42 ± 0.1 Hz vs. 4.75 ± 0.1 Hz in controls, p = 0.006). Sodium-glucose co-transporter-2 (SGLT2) expression was not detected in LV tissues. Conclusions: EMPA treatment reduced ventricular arrhythmia vulnerability and mitigated contractile dysfunction in the global I/R model while improving calcium cycling and mitochondrial redox by SGLT2-independent mechanisms.