Mechanisms of postsystolic thickening in ischemic myocardium: mathematical modelling and comparison with experimental ischemic substrates.

In the setting of regional ischemia, the "at-risk" myocardium exhibits a flow-related reduction in systolic thickening with a concomitant development of abnormal thickening after aortic valve closure (postsystolic thickening [PST]). With the introduction of high time-resolution ultrasonic-based strain/strain-rate imaging, this short lived phenomenon can be measured accurately in the clinical setting. The mechanisms underlying this ischemia-related PST are poorly understood and both active and passive etiologies have been proposed. This study aims at elucidating the potential mechanisms behind PST in the intact heart. A theoretical model, describing active force development, elasticity and segment interaction has been developed to simulate radial deformation during systole and iso-volumetric relaxation. Simulation results have been compared with experimental deformation curves obtained from postero-basal segments of a pig model undergoing varying controlled ischemic challenges. Three forms of regional ischemia could be simulated by varying the model parameters of the ischemic segments: (i) chronic regional hypo-perfusion (reduced and prolonged active force development; preserved elasticity); (ii) acute short-lived ischemia-temporary vessel occlusion (no active force development; preserved elasticity); and (iii) chronic myocardial infarction (no active force development; decreased elasticity). For all ischemic substrates, the simulated curves closely correlate to the deformation measured in the corresponding porcine models without the need for active force development during the occurrence of PST. This suggests that segment interaction is the key determinant in the development of PST. Thus, in all instances, at the time of its manifestation, ischemia-related PST could be explained in a unified way as a passive phenomenon that was the result of elastic segment interaction. Its occurrence originates from the end-systolic inhomogeneous state where neighboring segments have a different wall thickness. The occurrence of these differences at end-systole depends on the presence of regional differences within the ventricle in the magnitude and duration of the developed contraction force during the first part of systole, the elasticity of the ischemic segment and the left-ventricular pressure.