It is widely accepted that the autonomic nervous system can induce and/or worsen cardiac arrhythmias during bouts of myocardial ischemia and infarction. The purpose of the proposed experiments is, first, to define and then characterize how, when, and to what extent changes in nerve traffic, recorded from the discrete thoracic cardiac nerves of the dog, may disrupt the electrical stability of an infarcting heart. The hypothesis considers that the extent and severity of both the early and the delayed ventricular arrhythmias that occur during a myocardial infarction depend upon characteristic sequential changes in autonomic activities to the heart and that the nature and relative contributions of individual autonomic nerve activities are different but predictable. The hypothesis further considers that part of the mode of action of widely-used antiarrhythmic drugs is achieved through modulation of these complex autonomic influences. Simultaneous recordings of sympathetic and parasympathetic autonomic activities will and analyzed before and during a three hour occlusion of a coronary artery. All experiments will be performed in dogs because we can reliably identify all discrete thoracic cardiac nerves and because we can accurately determine their respective regional functional innervation patterns. These experiments will not only provide a quantitative assessment of the changing neural activities that accompany myocardial ischemia but, with this data, we will be able to determine when differences in nerve traffic to the ischemic versus the non-ischemic zone constitute an """"""""autonomic imbalance"""""""". Special experiments will then be performed using a variety of combinations of sympathetic and parasympathetic efferent nerve stimulation to mimic """"""""autonomic imbalance""""""""; before and during coronary artery occlusion. These experiments will, for the first time, quantitatively evaluate autonomic imbalance during acute myocardial ischemia. Also, we expect to prove or disprove whether and, if so, how often autonomic imbalance precipitates cardiac arrhythmias. Together with these experiments that are designed to examine how certain arrhythmic agents modulate autonomic imbalance we expect to generate important new information concerning the mode of action of these antiarrhythmic compounds. Knowledge of how antiarrhythmic changes influence the autonomic control of the heart will not only greatly facilitate the selection of the most appropriate antiarrhythmic compound but it will help minimize the proarrhythmic tendencies in these compounds.
