The right ventricular outflow tract (RVOT) is the main source of arrhythmias in the Brugada syndrome even as the exact mechanism remains unelucidated. We hypothesized that the RVOT structural discontinuities resulting in slower conduction as well as increased transmural gradients of depolarization and repolarization may be associated with arrhythmogenesis.
To test our hypothesis, we characterized the RVOT relative to the effect of different pharmacological interventions, endo/epi structural and functional differences, and transmural arrhythmia dynamics.
Donor human hearts (N=5) were procured for this study. The LCA and RCA were cannulated to enable RVOT perfusion and the tissue suspended vertically in a bath to enable simultaneous dual-sided optical mapping. RVOT was paced using a dynamic restitution protocol (S1S1) to assess rate dependence of APD under baseline conditions. The restitution protocol was repeated under different pharmacological conditions including acetylcholine(100mM), isoproterenol (100nM), lidocaine(15mM), and pinacidil (50mM). Arrhythmia was induced pharmacologically or using a 50Hz burst pacing.
Acetylcholine (267 ± 4 ms) did not have any statistically significant effect on the action potential duration compared to baseline conditions (271±7 ms) at 120 BPM, whereas isoproterenol (227 ± 11 ms) and pinacidil (128 ± 5 ms) shortened APD (p < 0.05). Epicardial (40 ± 4 ms) versus endocardial (50 ± 5 ms) dispersion of depolarization was not statistically significant under baseline conditions or after the different pharmacological interventions at 120 BPM. However, epicardial (65 ± 5 ms) versus endocardial (75 ± 5 ms) dispersion of repolarization was statistically significant at 120 BPM. Pharmacologically induced sustained arrhythmias were characterized by following wavefront and phase singularity dynamics: DF (10.3 ± 0.5 Hz), RI (0.36 ± 0.06), wavefront count (4 ±1), stable PS (7 ± 1), PS displacement (0.3 ± 0.12 cm), endo/epi Pearson correlation co-efficient (0.3 ± 0.1).
Our results suggest that there exists VT/VF endo/epi dyssynchrony in the RVOT (and RV), which is correlated with structural discontinuities (histology) and transmural dispersion of repolarization.