Fig. 6.

Antiarrhythmic effect of dapagliflozin in an in vivo large animal model of acute atrial fibrillation (AF). a Spontaneous beating frequency of atrial- and ventricular-like hiPSC-derived cardiomyocytes (hiPSC-CM), recorded with patch clamp under control conditions or exposition to dapagliflozin (10, 30, 100 µmol/L; atrial: n = 10–17; ventricular: n = 10–17). b Beating frequency (n = 3–12) and conduction velocity (n = 3–11) quantified from multi-electrode array (MEA) recordings of atrial-like hiPSC-CM monolayers relative to baseline values 15 min after application of dapagliflozin (1, 10, 30, 100 µmol/L) or the vehicle control. c Experimental protocol of a translational pilot study: Intracardiac electrophysiology (EP) catheters were inserted in anesthetized pigs and AF episodes were induced via atrial burst stimulation. If the AF episodes were stable within a 10 min control period, intravenous bolus administration of dapagliflozin (3 mg/kg body weight) or the appropriate solvent control (DMSO; dimethyl sulfoxide) was performed and the time to conversion to sinus rhythm (SR) was determined. If no conversion had occurred within 10 min, electrical cardioversion (eCV) was performed. Grey box: Representative EP recordings during burst stimulation and AF stabilization (left) and after administration of dapagliflozin (3 mg/kg body weight) showing cardioversion from AF to SR (right). d Conversion time in pigs treated with dapagliflozin (3 mg/kg body weight; n = 4) or the solvent control (n = 6). Box plots show the median and the interquartile range with whiskers ranging from minimum to maximum. The P-value was derived from Mann-Whitney-U-test. e Representative ECG recordings, obtained from pigs under control conditions and after treatment with dapagliflozin (3 mg/kg body weight). f Atrial parameters: P wave duration, duration from first intracardiac deflection to P wave peak and atrial conduction velocity in pigs under baseline conditions and after acute dapagliflozin treatment (3 mg/kg body weight; n = 4). g Ventricular parameters: ECG parameters, duration from QRS onset to first intracardiac deflection and ventricular conduction velocity in pigs under baseline conditions and after acute dapagliflozin treatment (3 mg/kg body weight; n = 4). Unless indicated otherwise, data are given as mean ± SEM and P-values were derived from Student´s t-tests