Dissociation of Membrane Potential and Intracellular Calcium during Ventricular Fibrillation

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Abstract
Introduction: The cardiac action potential (AP) and the intracellular Ca transient (CaT) are closely associated under normal physiological conditions, but not during ventricular fibrillation (VF). The purpose of this study was to determine whether this dissociation is directly related to the fast activation rate during VF. Methods and Results: We optically mapped AP and CaT simultaneously in nine isolated rabbit hearts. Pinacidil, a KATP channel opener, was used to shorten the action potential duration (APD) in order to capture tissue at fast pacing rates or to induce ventricular tachycardia (VT) comparable to VF activation rates. Mutual information (MI) was used to calculate the degree of AP and CaT coupling. Pinacidil (40 μM) infusion significantly shortened APD. The CL of VF without pinacidil averaged 77 ± 13 ms, whereas the shortest CL achieved during VT under pinacidil infusion was 76 ms. MIs during fast pacing (1.13 ± 0.15 bits) and fast VT (0.88 ± 0.18 bits) were higher than those during baseline VF (0.39 ± 0.11 bits), VF with pinacidil infusion (0.21 ± 0.07 bits) and VF after pinacidil washout (0.36 ± 0.15 bits). MIs during fast pacing or fast VT were higher than that of VFs at comparable dominant frequencies. Conclusions: CaT is closely associated with the AP during fast pacing and fast VT, but not during VF. The reduced MI during VF is not secondary to the fast rate of activation.

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