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Background: Local impedance (LI) at a distal tip of the ablation catheter can indirectly measure tissue temperature during radiofrequency catheter ablation (RFCA). LI decreases by RFCA, and a degree of LI drop is correlated with lesion size. However, data on the effects of catheter contact angle on LI parameters were scarce. This study aimed to evaluate the influence of catheter contact angle on LI change and lesion size in a porcine experimental model. Methods: Lesions were created on porcine myocardial left ventricles by the LI and Contact force(CF)-sensing ablation catheter (INTELLANAV STABLEPOINT™). Radiofrequency ablation was performed with a power of 30 watts and a duration of 30 seconds. CF (0, 5, 10, 20, and 30g) and catheter contact angle (30°, 45°, and 90°) were changed in each set (total 120 lesions, n=8 each). LI rise by catheter contact, LI drop by RF application, and lesion size (lesion width, surface width, and lesion depth) were evaluated. Results: The values of LI rise increased as CF increased. Regarding the difference of catheter angles, LI rise with 90° was lower than those with 30°. The LI drop also increased as CF increased in all contact angles. The LI drop with 90° was lower than those with 30° in CF 5, 10, 20, and 30 g, respectively. Maximum lesion width and surface width were smaller in 90° than those in 30°, whereas there were no differences in maximum lesion depth except for CF 5g. The approximate curves were well fitted with a quadratic equation in all angles on LI drop vs. maximum lesion width, and lesion depth. Conclusion: Under the same CF, the values of LI drop and lesion width in 90° were significantly lower than those in 30° despite lesion depths were not different among the three angles. LI drop correlates with lesion width and lesion depth at any angle, which may be a good predictor of lesion size.

Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors are agents that act by inhibiting glucose and sodium reabsorption in the proximal renal tubule which promotes urinary glucose excretion. More recently, significant benefit data of SGLT2 inhibitors in patients with heart failure, independent of the presence of type 2 diabetes has been reported. We have previously demonstrated that Canagliflozin (Cana), a SGLT2 inhibitor, reduced the ventricular effective refractory period in isoproterenol (ISP)-induced myocardial injury rat model accompanied with the suppression of reactive oxygen species and the elevation of ketone bodies, suggesting the effect of Cana on electrical cardiac remodeling. The direct effect of Cana to the cardiomyocytes and its underlying molecular mechanism was remained to be clarified. We therefore established an ISP-induced neonatal rat ventricular cardiomyocyte (NRVCM) in vitro model, pretreated with Cana and/or ketone bodies. Methods Primary NRVCM were isolated from Wistar rats, were pretreated by Cana with or without βOHB (the most abundant ketone body in circulation), followed by a stimulation of ISP (10μM). Cells without drug or ketone body pretreatment were used as control. We then analyzed its effect on cell viability, apoptosis, and mitochondrial membrane potential using MTT assay, TUNEL assay, and mitochondrial membrane potential assay, respectively. MTT assay was also performed with or without PI3k inhibitor, LY294002. The end-labeling of DNA fragmentation were labelled with FITC, followed by the nuclei counterstain with DAPI and were observed with confocal microscope. The apoptotic index was defined as the percentage of TUNEL positive cells / total nuclei. Results Cana rescued the reduction of NRVCM cell viability induced by ISP stimulation for 24 hours which was inhibited by LY294002 compared to cells without pretreatment. Interestingly, pretreatment of βOHB with or without Cana improved also the NRCVM cell viability whereas there was no significant difference between these two conditions or with cells treated with Cana only, suggesting the direct protective effect of Cana. In 48 hours of ISP stimulation, the apoptotic index intends to decrease in Cana and/or βOHB compared to cells without pretreatment (Figure 1). Although the mitochondrial function was maintained in Cana-pretreated cells compared to cells without pretreatment, there was no significant difference in βOHB-pretreated cells. Conclusions Cana has a direct protective effect on cardiomyocytes cell viability, apoptosis as well as the mitochondrial function impaired by ISP through the cell survival signaling PI3K/Akt pathway. This brings a new insight to the therapeutic target of cardiovascular disease. Funding Acknowledgement Type of funding sources: None.