Significance of inwardly directed transmembrane current in determination of local myocardial electrical activation during ventricular fibrillation

Ventricular fibrillation (VF) is the principal cardiac rhythm disorder responsible for sudden cardiac death in humans. The accurate determination of local cardiac activation during VF is essential for its mechanistic elucidation. This has been hampered by the rapidly changing and markedly heterogeneous electrophysiological nature of VF. These difficulties are manifested when attempting to differentiate true propagating electrical activity from electrotonic signals and when identifying local activation from complex and possibly fractionated electrograms. The purpose of this investigation was to test the hypothesis that the presence of a balanced inwardly and outwardly directed transmembrane charge, obtained from the ratio of the inward to outward area under the cardiac transmembrane current curve (-/+ I(m) area), could reliably differentiate propagating from electrotonic deflections during VF. To test this hypothesis, we applied a recently described technique for the in vivo estimation of the transmembrane current (I(m)) during cardiac activation. A 17-element orthogonal epicardial electrode array was combined with an immediately adjacent optical fiber array to record electrical and optically coupled transmembrane potential signals during VF. Recordings were obtained during electrically induced VF in six dogs to determine the I(m) associated with activation and the time course of repolarization, as well as unipolar electrograms and bipolar electrograms recorded at multiple center-to-center interelectrode distances from 0.2 to 3 mm. Propagating local activations were associated with the presence of an easily identified inwardly directed I(m), with a balanced inward and outward charge (-/+ I(m) area≃1.0). Electrotonic wave-forms lacked this inward I(m) (-/+ I(m) area≃0.0). Normal Na⁺-mediated inward currents were directly demonstrated to be responsible for some activations during VF.