Repolarization gradients in the intact heart: Transmural or apico-basal?

Controversies regarding the genesis of the T wave in the electrocardiogram and the role of midmural M cells in the intact heart include:
• whether transmural or apico-basal gradients in repolarization times are responsible for the T wave.
• whether M cells are involved in creating a transmural repolarization gradient thereby contributing to drug-induced Torsade de Pointes.In normal, intact canine and human hearts there is no significant transmural gradient in repolarization times. The T wave results primarily from apico-basal differences in repolarization times. Also, in the intact heart there is no midmural region of prolonged action potential duration. This contrasts with isolated preparations, such as the wedge preparation or myocardial slices or disaggregated myocytes in which M cells, with action potentials longer than those of endocardial and epicardial myocardium, can be found. This disparity in action potential duration probably results from partial uncoupling of myocardial cells in the regions where measurements are made, e.g., the cut surface of a wedge preparation. In regions of a wedge where cellular coupling is normal, or in isolated myocardial bundles or sheets, no evidence for M cells is detected. In some wedge preparations, a drug-induced large transmural repolarization gradient, involving M cells, can lead to Torsade de Pointes, possibly caused by so-called phase two reentry. In contrast, when a gradient of repolarization times of more than 100 ms was created in intact hearts, no evidence for reentry was found and no spontaneous arrhythmias occurred.In conclusion, in the intact heart, M cells appear not to contribute to repolarization gradients and arrhythmias. Furthermore, no significant repolarization gradients between endocardium and epicardium exist. The T wave in the body surface electrocardiogram is caused by apico-basal and anterior–posterior differences in repolarization times.