Several models will be used to study the characteristics of impulse propagation across inexcitable segments of cardiac tissue, and the relationship of the impaired conduction observed in such models to the generation of cardiac arrhythmias: parasystolic and reentrant extra-systoles and tachycardia. The models are 1) the sucrose gap preparation, adapted to mammalian Purkinje fibers, myocardial strips, and SA nodal tissue; 2) the """"""""ischemic"""""""" gap preparation, in which the central chamber is superfused with solutions mimicking the extracellular milieu in ischemic tissue; 3) a tandem preparation in which a gap preparation is allowed to interact with the exposed heart of an anesthetized dog; and 4) computer models incorporating the parameters derived from the biologic models. The computer models will be used to predict the patterns of arrhythmia to be expected when basic frequency, pacemaker activity, conductivity, excitability, etc are altered. The patterns will be compared with clinical records in an attempt to develop useful diagnostic criteria. The biologic models will be used to study the effects of changes in the ionic milieu, and the actions of drugs, antiarrhythmic and arrhythmogenic. The pharmacological tools will be used to assess the properties of the biologic models; conversely, the behavior of the models will be used to assess the action of the drugs on dysrhythmias of pacemaker origin (parasystole and """"""""modulated"""""""" parasystole) and of reentrant origin (""""""""reflected"""""""" reentry).
