Reentrant ventricular tachycardia in the non-infarcted myocardium is fundamentally a problem of propagation of three-dimensional vortex-like waves. The objective of this research proposal is to study the 3- dimensional organization and time evolution of vortex-like reentry initiated by premature stimulation in the open right or left ventricular wall of the coronary perfused rabbit ventricular myocardium. We will analyze the manifestation of reentry on the endocardial and epicardial surfaces using optical mapping techniques to determine the underlying three-dimensional structure of the activity. We will study also the role of anatomical factors such as variation in thickness of the myocardial wall, presence of large coronary vessels and presence of Purkinje fibers in the initiation and evolution of 3-dimensional reentry. In addition, to study the behavior in the thickness of the ventricles, we will develop a method for localizing point sources and 3-dimensional vortex filaments in the myocardial wall using transillumination data (front angle fluorescence). Our study will be based on the following hypotheses: i) vortex-like reentry in the form of scroll waves with varying-filament shapes, including I-, U-, L- or O-shapes, can be initiated by premature stimulation; the particular shape of the scroll wave may be controlled by the size and geometry of the stimulating electrode, as well as on the amplitude and coupling interval of the stimulus; ii) the initial size and geometry of the filament are responsible for varying dynamics of vortex- like reentry observed in the same preparations at various amplitudes and coupling intervals of the premature stimulus iii) 3-dimensional vortices are in general unstable, their stabilization being a result of anchoring to macroscopic discontinuities. We will use a voltage sensitive dye and a dual video imaging system, as well as computer modelling to test these hypotheses. Two video cameras will be used to record electrical wave propagation simultaneously from the endocardial and epicardial surfaces of the open right or left ventricle and to study the mechanisms of initiation, dynamics and termination of scroll waves. Computer modelling of propagation in 3-dimensions will be used to develop stimulation protocols which will be used for the initiation of reentry in the optical mapping experiments; to gain insight into the mechanisms of 3-dimensional vortex- like reentry; to analyze the role of structural factors on stability and dynamics of 3-dimensional reentry; and to study the manifestation of various forms of 3-dimensional reentry in surface and transillumination optical mapping experiments. The proposed work is expected to provide definite information regarding the relationship between 3-dimensional scroll wave reentry and ventricular tachycardia in the isolated healthy heart. Such information should lead to a better understanding of the mechanisms of monomorphic and polymorphic ventricular tachycardias, and will facilitate the interpretation of surface and course-resolution intramural mapping studies of such arrhythmia mechanisms. The overall results should pave the way to a mechanistic basis for the differential diagnoses of arrhythmia in the 3-dimensional myocardium. Ultimately, it is hoped that the knowledge derived from these studies will be applicable to the understanding and rational treatment of reentrant arrhythmias in man.
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