SAR296968, a Novel Selective Na+/Ca2+ Exchanger Inhibitor, Improves Ca2+ Handling and Contractile Function in Human Atrial Cardiomyocytes

Figures

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  Figure 1. Ca2+ sparks measurements in isolated human atrial myocytes. The numbers indicated are numbers of patients. The data points represent individual patients. Each data point was calculated as a mean from several cells within each patient. Ca2+ spark frequency is reduced by SAR296968, original line scans are shown in (A), and mean data in (B). Fluo-4 transient amplitude after rapid caffeine application is shown in (C), the transient amplitude is significantly increased at 3 µM, original caffeine transients in (D). The p-values are denoted above the corresponding groups, RM-mixed effects analysis with Bonferroni post-hoc test.

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  Figure 2. The numbers indicated are the numbers of patients. The data points represent individual patients. Each data point was calculated as the mean from several trabeculae within each patient. The mean data per patient shown for isolated human atrial trabeculae in steady-state (1 Hz) exposed to SAR296968. The diastolic tension is reduced by SAR296968 (A). The fractional difference in the developed tension compared to the vehicle was significantly increased (B), # indicates a significant difference from zero). Developed tension after 30 s rest (post-rest test) was significantly increased by SAR296968 at 3 µM (C). The original traces are shown in (D). The p-values are denoted above the corresponding groups, RM-mixed effects analysis with Bonferroni post-hoc test.

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  Figure 3. The numbers indicated are numbers of patients. The data points represent individual patients. Each data point was calculated as the mean from several cells within each patient. The mean data per patient for action potential characteristics were measured in isolated human atrial myocytes by the whole-cell patch clamp technique. (A) resting membrane potential, (B) AP amplitude, and (C) action potential duration (APD) at 90% of maximum repolarization were unaffected by SAR296968. The original traces are shown in (D). The p-values are denoted above the corresponding groups, RM-mixed effects analysis with Bonferroni post-hoc test.