IVA decreased spontaneous intrinsic HR in isolated rabbit hearts
The HR and PR intervals at baseline of the isolated rabbit hearts were 161.90 ± 2.81 bpm and 42.84 ± 3.02 ms, respectively (n=24). IVA (0.1-10 μM) reduced the HR by 83.24 ± 7.30 in a concentration-dependent manner from 161.90 ± 2.81 bpm to 81.14±5.15 bpm at concentration of or higher than 0.1 µM and prolonged the PR interval from 44.12 ± 3.77 ms to 61.96 ± 3.50 ms at concentration of or higher than 1 µM (n=8, p < 0.05 ; Fig 1 and Table 1). At concentrations of 6 and 10 μM, IVA prolonged QT interval and QRS duration from 212.00 ± 3.56 ms and 62.00 ± 2.03 ms to 218.49 ± 2.87 and 76.22 ± 15.19, and 220.16 ± 6.94 and 80.46 ± 7.33 ms, respectively (n=8,p < 0.05 ). ATX-II (2 nM) and ACh (0.3 µM) caused a small decrease in HR from 4.87 ± 1.59 and 10.34 ± 3.89 bpm, respectively. However, in the continued presence of either ATX-II or ACh, IVA caused a smaller decrease in HR by 58.07 ± 6.09 bpm and 49.14 ± 5.50 bpm (p < 0.05 vs. in absence of either ATX-II or ACh,Fig 1).