The isolated ventricular wedge preparation: A valid proof of relevance

Abstract

b ( o a l P t A What exactly are the electrophysiologic bases accountable for the various ECG waves? In the search for an answer to this fundamental question (in particular with regard to the ST segment and the T wave), 16 years ago Yan and Antzelevitch reported the creation of an innovative experimental model—the isolated, coronary-perfused canine ventricular wedge preparation. The thought was to use it as a tool for studying the temporal correlation between action potentials recorded across the ventricular wall and the corresponding “transmural” (pseudo) ECG. In that the ECG electrodes are placed facing the epicardial (Epi [ ]) and endocardial (Endo [ ]) surfaces of these preparations, stimulation applied to Endo results in a depolarization wavefront in the Endo-to-Epi direction, which, in turn, accounts for the electrocardiographic R wave. Conversely, since the repolarization wavefront follows the same direction, the T wave is upright. At the start, a well-defined parameter (of potential clinical relevance) readily derived from the ECG of these isolated tissues. I am referring to the “terminal portion of the T wave,” which is (certainly in the wedge) an expression of transmural dispersion of repolarization and, therefore, an index of vulnerability to arrhythmogenesis. The critical observation is that its peak appreciably coincides with full repolarization of the Epi and its end with full repolarization of the sub-Endo (M-cell) action potentials. This time interval was understandably called Tpeak-Tend. The article by Liu et al in this issue of HeartRhythm eports the results of an encouraging, truly blinded validaion study that further highlights the capability of the wedge reparation—in this case isolated from the left ventricle of he rabbit heart. In their study, not only the proarrhythmic isk of several cardiac and noncardiac drugs could be quanified, but their underlying mechanisms of action could also e “blindly” recognized. In essence, their experimental proocols were designed to differentiate the effect of 14 comounds (at various concentrations and pacing rates) on the asis of their effects on the QRS, QT, Tpeak-Tend, and