It has been argued that the canine left ventricular wedge is too small a sample and does not reflect what might happen in an intact heart.27
This prompted us to develop an experimental model where we use the intact rabbit LV instead of a wedge. In this model, we tested the relative role of the transmural versus the apico-basal voltage gradient in the genesis of the T wave. We elected to use the rabbit LV instead of the dog for several reasons. First, as shown in , the isolated rabbit LV is perfused by cannulating the left main coronary artery that allows us to use the complete left ventricular tissue in the experiment and it ensures that the preparation is well perfused. Because it includes the whole ventricle it allows us to record the transmural and the apico-basal voltage gradient simultaneously. Secondly, cells with electric resemblance to the M cells are located in the endocardium of the rabbit LV,28,29
so that it is technically easier to simultaneously record action potentials from the endocardium and epicardium. The action potential recordings obtained from intact epicardial and endocardial surface eliminates the possibility of injury and uncoupling due to dissection. Some have proposed that transmural dispersion of repolarization seen in the small canine wedge preparation may be related to injury and uncoupling of the cells because the action potential is recorded from a transected subendocardial surface.30,31
Realistically the cut surface constitutes only an extremely small fraction of the entire wedge preparation that should have little influence on the pseudo-ECG. In any case, the arterially-perfused rabbit LV is devoid of such a confounding factor.
Figure 2 A, Schematic presentation of the arterially perfused rabbit LV. LM, left main coronary artery; LAD, left anterior descending coronary artery; LCD, left circumflex coronary artery. B, Schematic presentation of simultaneous recording of 4 sets of action (more ...)
The arterially perfused rabbit LV was prepared in a similar way as the rabbit left ventricular wedge.28,32–34
To accomplish this, as shown in , we recorded the endocardial and the epicardial transmembrane action potentials simultaneously from the apical and the basal areas of the rabbit LV. Two pseudo-ECGs were recorded: one recorded transmurally and another across the apico-basal axis of the left ventricular wall. It is important again to emphasize that the pseudo-ECGs were recorded in the volume conductor in which the electrodes were placed at least 2 cm from the epicardial and endocardial surfaces, or from the apex and base of the isolated LV. After control recording at a basic cycle length of 1000 ms, 0.1 μ
mol/L cisapride at was infused to determine if it has any preferential effects on epicardial/endocardial or apical/basal cell action potential.
Representative recordings from these experiments are shown in . Under control conditions, the APD of apical cells (both endocardial and epicardial surfaces) was slightly longer than the APD of the respective basal cells; however, the difference was not statistically significant. On the other hand, both at the apical and the basal recording sites, the APD of the endocardial cells were consistently longer than the epicardial cells and the results were statistically significant. This difference in the time course of repolarization of the epicardial and endocardial cells, ie, the transmural dispersion of repolarization, caused the inscription of the T wave in the pseudo-ECG recorded across the transmural axis. In both apical and basal recording sites, the peak of the T wave was coincident with the end of repolarization of the epicardium and the end of T wave was coincident with the end of repolarization of the endocardium. In contrast, the pseudo-ECG recorded along the apico-basal axis had T waves that were either flat or negative.
Figure 3 A, A representative recording from the rabbit LV showing well-defined T waves in pseudo-ECGs recorded across the transmural axis under control conditions and after infusion of cisapride. Note that the pseudo-ECG recorded across the apico-basal axis fails (more ...)
After infusion of the IKr blocker cisapride, the QT interval prolonged with a preferential prolongation of APD of the endocardial cells as compared with the epicardial cells across the entire LV, leading to an increase in TDR and a corresponding increase in the duration of descending limb of the T wave, ie, the Tp-e interval. Cisapride increased the APD of the apical cells slightly more than the basal cells; however the observed difference was not statistically significant. Once again, the apico-basal pseudo-ECG showed nonspecific T wave morphologies and we were unable to identify any corelation between the morphological changes in action potential and the pseudo-ECG. Findings were reproduced in 4 similar experiments. Composite data are shown in .
The canine left ventricular wedge spans 5 cm of the LV across the apico-basal axis. A decade of experience with this preparation confirmed that there is no significant dispersion of repolarization across the apico-basal axis in such a small segment of LV.13
Does this hold true in an entire canine LV? This issue was elegantly addressed in recent work by Rosenbaum and coworkers35
in canine hearts using optical mapping technique. In this study investigating the physiological basis of T wave memory, 3 wedge preparations were used from anterior, lateral, and posterior surface of canine LV, respectively. Action potentials were recorded with optical mapping technique from all 3 wedge preparations. The dispersion of repolarization was calculated across the transmural axis of each wedge (ie, TDR) and also between 2 LV wedges (ie, segmental dispersion of repolarization). The transmural pseudo-ECG was calculated by subtracting the action potentials from epicardial cells and M cells. The segmental ECG was calculated by subtracting action potentials of M cells recorded from 2 different LV wedges/segments after accounting for known activation time between segments. The results showed the presence of TDR in all 3 LV wedges, but there was no significant segmental dispersion of repolarization. Both the measured and the calculated transmural Pseudo-ECGs showed upright T wave that matched the polarity of in vivo ECG. However, the calculated segmental ECG failed to register any T wave. These observations outlined above, clearly demonstrate the prominent role of TDR in the electrocardiographic inscription of the T wave, both in the rabbit and canine LV.