Objective: To investigate the mechanism of pause dependent torsade de pointes (TdP) in long QT (LQT) conditions.
Methods: Optical mapping was used to measure transmural action potentials from the arterially perfused left ventricular canine wedge preparation. D-sotalol and ATX-II were administered to mimic LQT 2 and LQT 3, respectively.
Results: In LQT models, the pause significantly enhanced M cell action potential (control group Steady state stimulation S1S1: (291 +/- 27) ms, after pause: (307 +/- 28) ms, P > 0.05; LQT 2 S1S1: (356 +/- 20) ms, after pause: (381 +/- 25) ms, P < 0.05; LQT 3 S1S1: (609 +/- 92) ms, after pause: (675 +/- 98) ms P < 0.05), dispersion of transmural repolarization (control group S1S1: (24 +/- 6) ms, after pause: (27 +/- 6) ms, P > 0.05; LQT 2 S1S1: (35 +/- 9) ms, after pause: (46 +/- 11) ms, P < 0.05; LQT 3 S1S1: (121 +/- 85) ms, after pause: (171 +/- 98) ms, P < 0.05) and the M cell island-like distribution more clearly compared to baseline pacing. Pause dependent early afterdepolarizations (EADs), EAD-induced triggered activity and TdP more likely occurred under LQT 3 condition (82%, P < 0.05). The triggered beat after pause often broke through at the margin of M cells island where the repolarization gradients was maximal. The unidirectional conduction block and slow conduction were observed vividly at this region.
Conclusion: These data suggest that M cells island plays an important role in origination and maintenance of pause dependent TdP.