The major objective of this renewal proposal is to continue studies of experimentally induced chronic electrophysiologic abnormalities in feline cardiac tissue. We plan to study: (1) electrophysiology and arrhythmogenesis in tissue having chronic electrophysiologic abnormalities after healing for 3 months after acute ischemic injury, and in tissue in which acute ischemic injury has been superimposed upon chronic electrophysiologic abnormalities; (2) the effect of membrane-active drugs upon electrophysiologic properties of tissue which had healed after ischemic injury; (3) the electrophysiologic consequences of superimposition of acute ischemic injury on chronic electrophysiologic abnormalities produced by experimental chronic pressure overload of the left ventricle; (4) the interaction between autonomic nervous system activity and healed ischemic tissue; and (5) the extent to which chronic electrophysiologic abnormalities related to structural changes. Cellular electrophysiologic abnormalities relate to structural changes. Cellular electrophysiologic studies will be performed on left ventricular preparations containing areas of healed ischemic injury and surrounding normal tissue, with or without superimposed acute ischemic injury. The studies will employ both transmembrane action potential recording techniques and surface electrogram techniques. Multiple recordings will be used to study patterns of activation, with particular emphasis on the initiation, perpetuation, and termination of reentrant circuits in isolated tissue. The same techniques will be used to study the influence of membrane-active antiarrhythmic agents and ionic interventions on ischemic tissue. The interaction between autonomic nervous system activity and ischemic injury will be studied by means of determining epicardial refractory periods before, during, and after sympathetic and parasympathetic stimulation. These studies will determine the extent to which autonomic nervous system factors interact with local myocardial factors in problems related to electrophysiologic instability. The relationship between structural changes in injured tissue and electrophysiologic abnormalities will be studied by means of both light microscopy and scanning electronmicroscopy. The studies will emphasize structure at the electrophysiologic border between healed ischemic tissue and normal tissue.
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