Purkinje-myocardial reentry in ischemia and infarction

University Of Alabama At Birmingham, Birmingham AL

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Abstract

The contribution of the heart's specialized conduction system to arrhythmia initiation is not completely understood. While Purkinje fibers are considered a potent source for the initiating extrasystoles in focal and reentrant ventricular arrhythmias, recent suggests a contribution of Purkinje-myocardial reentry to polymorphic tachycardia that can precede fibrillation and sudden death. Our main objective is to investigate how reentrant circuits distribute between the peripheral conduction system and overlying myocardium during early cycles of sub-endocardially- induced ventricular arrhythmias. We believe those circuits circumscribe functional centers that are primarily located on the peripheral conduction system-myocardial interface, where the two components are weakly coupled via the system of discrete Purkinje-ventricular junctions (PVJs). We hypothesize this arrangement establishes peripheral conduction system and myocardial wavefronts that are out of phase with one another, which places critical importance about the ability of premature action potentials to propagate from peripheral conduction system to myocardium, i.e. antegrade PVJ conduction, for reentry maintenance. Antegrade PVJ conduction is inherent discontinuous because the myocardium imposes a large electrical load on peripheral conduction system. Experiments to test this hypothesis will use 1056-channel electrical mapping from perfused rabbit right ventricular free wall surfaces. Companion stimulations will incorporate membrane equations for ionic currents into detailed grids replicating the interface. The project has two aims. The first aim is to establish the relationship between antegrade PVJ PVJ conduction and subendocardially induced ventricular arrhythmias in macroscopically normal hearts. The second aim is to correlate regional acute ischemia and healing myocardial infarction with peripheral conduction system participation during subendocardially induced ventricular tachycardia.