Abstract

ST elevation on an electrocardiogram is a hallmark of acute transmural ischemia. However, the underlying mechanism remains unclear. We hypothesized that high ischemic sensitivities of epicardial adenosine triphosphate-sensitive potassium (IKATP) and sodium (INa) currents play key roles in the genesis of ST elevation. Using a multi-scale heart simulation under moderately ischemic conditions, transmural heterogeneities of IKATP and INa created a transmural gradient, opposite to that observed in subendocardial injury, leading to ST elevation. These heterogeneities also contributed to the genesis of hyper-acute T waves under mildly ischemic conditions. By contrast, under severely ischemic conditions, although action potentials were suppressed transmurally, the potential gradient at the boundary between the ischemic and normal regions caused ST elevation without a contribution from transmural heterogeneity. Thus, transmural heterogeneities of ion channel properties may contribute to the genesis of ST–T changes during mild or moderate transmural ischemia, while ST elevation may be induced without the contribution of heterogeneity under severe ischemic conditions.

Highlights

  • Despite its long history, the electrocardiogram (ECG) remains an indispensable tool for diagnosis of heart diseases such as arrhythmias and myocardial ischemia

  • ST segment elevation during acute myocardial infarction requires the injury current to flow in the opposite direction [12, 13, 24], which can be caused by greater depression of the epicardial action potential

  • In the present study, using a multi-scale heart simulation, we examined whether such a gradient is possible, and if so, how it contributes to the genesis of ST elevation

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Summary

Introduction

The electrocardiogram (ECG) remains an indispensable tool for diagnosis of heart diseases such as arrhythmias and myocardial ischemia. In cases of angina pectoris, in which ischemia usually occurs in the subendocardial region of the ventricular wall, the developed potential gradient generates the current of injury flowing to the normal epicardial area during diastole, resulting in a positive potential of the TQ-segment of the ECG. ST segment elevation during acute myocardial infarction requires the injury current to flow in the opposite direction [12, 13, 24], which can be caused by greater depression of the epicardial action potential. Despite their favorable anatomical location for coronary perfusion, the severe effects on epicardial cells suggest that they should exhibit properties

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