Toward prediction of the local onset of alternans in the heart

A beat-to-beat variation in the cardiac action potential duration is a phenomenon known as alternans. Alternans has been linked to ventricular fibrillation, and thus the ability to predict the onset of alternans could be clinically beneficial. Theoretically, it has been proposed that the slope of a restitution curve, which relates the duration of the action potential to the preceding diastolic interval, can predict the onset of alternans. Experimentally, however, this hypothesis has not been consistently proven, mainly because of the intrinsic complexity of the dynamics of cardiac tissue. It was recently shown that the restitution portrait, which combines several restitution curves simultaneously, is associated with the onset of alternans in isolated myocytes. Our main purpose in this study was to determine whether the restitution portrait is correlated with the onset of alternans in the heart, where the dynamics include a spatial complexity. We performed optical mapping experiments in isolated Langendorff-perfused rabbit hearts in which alternans was induced by periodic pacing at different frequencies, and identified the local onset of alternans, B^onset. We identified two regions of the heart: the area that exhibited alternans at B^onset (1:1 _alt) and the area that did not (1:1). We constructed two-dimensional restitution portraits for the epicardial surface of the heart and measured the spatial distribution of three different slopes (the dynamic restitution slope, S^RP_dn, and two local S1-S2 slopes, S₁₂ and S^max₁₂) separately for these two regions. We found that the S¹² and S^max₁₂ slopes differed significantly between the 1:1_alt and 1:1 regions just before the onset of alternans, and S^RP_dyn slopes were statistically similar. In addition, we found that the slopes of the dynamic restitution curve S_dyn were also statistically similar between these two regions. On the other hand, the quantitative values of all slopes were significantly different from the theoretically predicted value of one. These results demonstrate that the slopes measured in the restitution portrait correlate with the onset of alternans in the heart.