Infusion with 15 nM ISO increased the IHI from 1.2 ± 0.03 to 1.7 ± 0.03 at constant pacing rate (4.5 Hz, n = 6, p < 0.05, figure 3a). Compared with an orderly spread of excitation beginning with localized stimulation-induced activation, the excitation pattern at the first beat of AF resulted in an inhomogeneous mode, with the IHI increased by 108% (from 1.2 ± 0.03 to 2.6 ± 0.05 ms) (n = 6, p < 0.05, figure 3).

Furthermore, both RAN and ELEC at 10 µM decreased IHI from 1.7 ± 0.03 to 1.2 ± 0.04 and 1.3 ± 0.02 at fixed rate pacing and from 2.6 ± 0.05 to 1.6 ± 0.04 and 1.7 ± 0.04 at the first beat of AF, respectively (n = 6, p < 0.05; figure 3).

Figure 3. Effects of drugs on inhomogeneity of atrial conduction. (a) The index of inhomogeneity (IHI) at a fixed rate (baseline) and at the first beat of AF in hearts treated with either isoproterenol (ISO; 15 nM) alone or ISO + ranolazine (RAN; 10 μM, n = 6), ISO + eleclazine (ELEC; 10 μM, n = 6) or ISO + KN-93 (3 μM, n = 6). (b) Representative examples of epicardial conduction properties of left atrium by multi-electrode array in the absence (i) and presence (ii) of ISO at baseline, and treated with ISO (iii) and ISO + ELEC (10 μM) (iv) at the first beat of AF. *p < 0.05 versus control (CTL); **p < 0.05 versus ISO at baseline; ***p < 0.05 versus ISO + drugs at the first beat of AF.

The Royal Society Publishing

https://doi.org/10.1098/rstb.2022.0163