Figure 1.
Ivabradine (iva) prolongs survival among dnNRSF‐Tg (Tg) mice. A, Representative If currents recorded in ventricular myocytes from a Tg mouse in the presence (red line; 2 minutes after the application of iva) and absence of iva (black line). Inward‐rectifier K+ current was suppressed by 0.5 mmol/L BaCl2. Pulse protocol is shown in the top. B, Relative If amplitudes (%) measured at −140 mV in the absence (vehicle, indicated as veh) and presence of iva (+iva). A mean relative If amplitudes (%) in the absence of iva was assigned a value of 100 (n=6 each). *P<0.05 vs vehicle. The Wilcoxon signed‐rank test was used for the analysis. C, Heart rates in wild‐type (WT) and Tg mice at 20 weeks of age, with and without 12 weeks of iva treatment (n=9 for untreated control WT, n=5 for WT with iva, n=10 for untreated control Tg and n=6 for Tg with iva). Kruskal–Wallis nonparametric ANOVA followed by the Bonferroni correction was used for analysis among the 4 groups. NS, not significant. Graphs are shown in dot plots. D, Kaplan–Meyer survival curves for Tg mice, with or without ivabradine. Drug treatment began when the mice were 8 weeks of age and lasted 24 weeks: *P<0.05 (n=54 for Tg without drugs [control], 28 for Tg with ivabradine). E through G, Body weights (BW) (E), heart weight‐to‐body weight ratios (HW/BW) (F) and lung‐to‐body weight ratios (LW/BW) (G) in 20‐week‐old WT and Tg mice, with or without iva (for BW and HW/BW comparisons, n=9 for untreated WT, n=4 for WT treated with iva, n=11 for untreated Tg, and n=6 for Tg treated with iva; for LW/BW comparisons, n=3 in each group). Kruskal–Wallis nonparametric ANOVA followed by the Bonferroni correction was used for analysis among the 4 groups. *P<0.00833. NS, not significant. Data in E through G are shown as dot plots. dnNRSF‐Tg indicates dominant‐negative form of neuron‐restrictive silencer factor transgenic mice; ANOVA, analysis of variance; cont, control.