The broad long term objective is to determine the electrophysiological mechanisms causing reentrant ventricular tachyarrhythmias in healing infarcts and the anatomical basis for these arrhythmias. Since reentrant ventricular tachyarrhythmias cause incapacitation and sudden death an improved understanding of their mechanisms is predicted to assist in the development of better therapeutic interventions. The specific aims are to test a series of hypotheses concerning proposed influences of infarct structure, in particularly the location and geometrical arrangement of surviving cardia muscle fibers, on electrical impulse propagation. The hypotheses state that 1) The formation of a thin sheet of muscle in an infarcted will cause reentry when the muscle fibers comprising the sheet are arranged parallel to each other. 2) Reentry results in this sheet because of the slow conduction that occurs transverse to the long axis of the myocardial fibers-anisotropic reentry. Action potential need not be abnormal. 3) Reentry caused by tissue anisotropy (parallel orientation) has special properties that are different from other types of functional reentry (leading circle). In particularly the circuits have an excitable gap. 4) Anisotropic properties vary among infarcts and it is only in hearts in which there is a high degree of nonuniform anisotropy that sustained ventricular tachycardia occurs. These hypotheses will be tested by using different electrosphysiological mapping techniques (electrical and optical) to plot excitation in myocardial infarcts caused by freezing part of the left ventricular wall. Transmembrane action potentials will also be recorded with glass microelectrodes form cardiac cells in reentrant circuits. Mophometric analysis of cardiac fiber bundle size, orientation and separation will be correlated with the electrical measurements to learn the anatomical basis for the electrical properties.
NIH ExPorter
NIH ExPorter