Activation Rate Gradients During Early Ventricular Fibrillation Are Determined By Transmural Ik(atp) Heterogeneity
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HRS Meeting Name
Heart Rhythm On Demand 2013
Edward J. Vigmond, PHD
Poster Session III
Session Date and Time
Thursday, May 9, 2013, 2:00 PM
Introduction: Transmural activation rate gradients develop during early VF with higher frequencies colocalized with Purkinje System (PS) terminations. These gradients are suppressed by prior application of glibenclamide (an IK(ATP) blocker) which also leads to spontaneous defibrillation. However, it remains unclear whether the PS contributes to AR heterogeneity. Chemical ablation of the PS is possible experimentally but is not selective for the PS and destroys endocardium as well. We sought to use detailed computer simulations to separate IK(ATP) from PS contributions to AR gradients during VF.
Methods: Ventricular computer models with either non-ungulate (endocardial) or ungulate (sub-epicardial) PS termination were constructed. Physiological IK(ATP) gradients were implemented and several seconds of VF were induced.
Results: Significant AR gradients were observed in VF only for large transmural IK(ATP) gradients (see figure, bullseye AR insets). The critical determinant of AR gradient formation was refractoriness in low-IK(ATP) regions, leading to longer action potentials which blocked propagation from high-IK(ATP) regions. The PS was not invovled in establishing or maintaining AR gradients, but, increased AR heterogeneity on the endocardium or epicardium. Simulated glibenclamide application terminated VF within, at most, a few seconds, in accordance with previous experiments demonstrating cardioprotective properties of pretreatment with glibenclamide.
Conclusions: An important factor underlying transmural AR gradients during early VF is differential IK(ATP) activation. We conclude that IK(ATP) modulation would be a stronger target for VF termination than a Purkinje based strategy.