Transmural dispersion in LQT3 and arrhythmogenesis.

At the end of the 19th century Einthoven described the configuration of the human ECG [1] and in later papers he elaborated on the magnitude and direction of its components [2]. From an intellectual point of view it is in fact unacceptable that we still do not know exactly how the T wave emerges. More precisely, we may understand how (dispersion in) repolarization within the ventricles transforms into the T wave in the ECG, but we have to live with the fact that we cannot translate the T wave into dispersion in repolarization. Biophysicists recognize this as Fthe inverse problem_ [3] and it might be that it will never be solved, because multiple cardiac repolarization orders may translate into one and the same T wave. This may be based on the fact that 90% of all signals during repolarization are canceled [4]. There is wide recognition that dispersion in repolarization is proarrhythmogenic. Studies which aim at elucidation of the relation between local repolarization differences and the T wave are important in our understanding of arrhythmias. We have read with interest the paper by Peter Milberg and colleagues in the February 2005 issue of Cardiovascular Research [5]. The authors have mimicked LQT3, based on mutations in the gene encoding the fast inward Na current, in a rabbit model by administration of veratridine, which interferes with inactivation of these channels leading to inward current during the plateau phase of the action potential. Under normal conditions these channels are closed during the plateau phase. It logically follows that this leads to prolongation of the action potential as shown in Fig. 1 and Table 1 [5] and we may assume that the QT intervals were