The mechanism of pause-induced torsade de pointes in long QT syndrome.
BACKGROUND
Torsade de pointes (TdP), is often preceded by a short-long cycle length sequence. However, the causal relationship between the pause associated with a short-long cycle length sequence and TdP is not completely understood. This study tests the hypothesis that a pause enhances both dispersion of repolarization and EAD formation; however, EADs that form where APD is longest will be less likely to initiate TdP.


RESULTS
We used optical mapping to measure transmural action potentials from the canine left ventricular wedge preparation. D-sotalol and ATX-II were used to mimic LQT2 and LQT3, respectively. The pause significantly enhanced mean APD (from 356 +/- 20 to 381 +/- 25 msec in LQT2, P < 0.05; from 609 +/- 92 to 675 +/- 98 msec in LQT3, P < 0.05) and transmural dispersion (from 35 +/- 9 to 46 +/- 11 msec in LQT2, P < 0.05; from 121 +/- 85 to 171 +/- 98 msec in LQT3, P < 0.05) compared to steady state pacing. Under LQT3 condition EADs, EAD-induced triggered activity, and TdP were more likely to occur following a pause. Interestingly, the triggered beat following a pause always broke through at the region of maximum local repolarization gradient.


CONCLUSIONS
These data suggest that a pause accentuates transmural repolarization gradients and facilitates the formation of EADs and EAD-induced triggered activity. In contrast to our hypothesis, the findings of this study support the concept that M-cells (where APD is longest) can play an important role in both the origination of EAD-induced triggered activity and unidirectional block associated with TdP.
Liu
Jinqiu
J
The Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University, Cleveland, Ohio 44109-1998, USA.
Laurita
Kenneth R
KR
D000200:Action Potentials; D000818:Animals; D018780:Body Surface Potential Mapping / Q000379:methods*; D004285:Dogs; D004562:Electrocardiography; D006329:Heart Conduction System / Q000503:physiopathology*; D008133:Long QT Syndrome / Q000175:diagnosis / Q000503:physiopathology*; D016171:Torsades de Pointes / Q000175:diagnosis / Q000503:physiopathology*; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000503:physiopathology*