Role of structural barriers in the mechanism of alternans-induced reentry

Previously, using an animal model of T-wave alternans in structurally norma l myocardium, we demonstrated that repolarization can alternate with opposi te phase between neighboring myocytes (ie, discordant alternans), causing s patial dispersions of repolarization that form the substrate for functional block and reentrant ventricular Fibrillation (VF). However, the mechanisms responsible for cellular discordant alternans and its electrocardiographic manifestation (ie, T-wave alternans) in patients with structural heart dis ease are unknown. We hypothesize that electrotonic uncoupling between neigh boring regions of cells by a structural barrier (SB) is a mechanism for dis cordant alternans. Using voltage-sensitive dyes, ventricular action potenti als were recorded from 26 Langendorff-perfused guinea pig hearts in the abs ence (ie, control) and presence of an insulating SE produced by an epicardi al laser lesion. Quantitative analysis of magnitude and phase of cellular a lternans revealed that in controls, action potential duration alternated in phase at all ventricular sites above a critical heart rate (269+/-17 bpm), ie, concordant alternans. Also, above a faster critical heart rate thresho ld (335+/-24 bpm), action potential duration alternated with opposite phase between sites, ie, discordant alternans. In contrast, only discordant but not concordant alternans was observed in 80% of hearts with the SE, and dis cordant alternans always occurred at a significantly slower heart rate (by 68+/-28 bpm) compared with controls. Therefore, the SE had a major effect o n the alternans-heart rate relation, which served to facilitate the develop ment of discordant alternans. Whether a SE was present or not, discordant a lternans produced considerable increases (by approximate to 170%) in the ma ximum spatial gradient of repolarization, which in turn formed the substrat e for unidirectional block and reentry. However, by providing a structural anchor for stable reentry, discordant alternans in the presence of a SE led most often to sustained monomorphic ventricular tachycardia rather than to VF, whereas in the absence of a SE discordant alternans caused VF. SBs fac ilitate development of discordant alternans between cells with different io nic properties by electrotonically uncoupling neighboring regions of myocar dium. This may explain why arrhythmia-prone patients with structural heart disease exhibit T-wave alternans at lower heart rates. These data also sugg est a singular mechanism by which T-wave alternans forms a substrate for in itiation of both VF and sustained monomorphic ventricular tachycardia.