Pharmacological modification of arrhythmias after experimentally induced acute myocardial infarction. Drugs acting on the nervous system.

The adrenergic neurohumors, when present locally in the myocardium in high concentrations, can produce a variety of cardiac arrhythmias which may develop into ventricular fibrillation (VF). Of particular importance are the arrhythmias observed immediately after experimentally induced acute myocardial infarction (AMI). Fatal VF, often seen to occur after acute coronary occlusion in the canine heart, may be related to the release of endogenous catecholamines, and a similar phenomenon might be responsible for sudden coronary death (SCD) in man. If adrenergic amines play a vital role in the development of arrhythmias and VF in response to acute myocardial ischemia, then it is conceivable that pharmacological means may be undertaken in an attempt to prevent the release of the adrenergic neurotransmitter or to prevent its arrhythmogenic actions by specific blockade of cardiac beta-adrenergic receptors. Drugs that have a central site of action and are capable of producing a decrease in sympathetic outflow might also play a valuable role in the prevention of arrhythmias and SCD. While the activity of the autonomic nervous system can modify the type and severity of arrhythmias resulting from AMI, existing pharmacological agents have little to offer in preventing the potential adverse effects of adrenergic stimulation without compromising the level of consciousness or cardiovascular function through the removal of adrenergic support to the heart. It would seem more beneficial to direct drug therapy at the electrophysiological defect in the myocardium in an effort to prevent arrhythmias and fatal VF. While currently available antiarrhythmic agents fail to achieve the desired effect, the recent evidence dealing with the quaternary ammonium derivatives of propranolol, lidocaine, and bretylium provides some hope for the future development of drugs with antiarrhythmic as well as antifibrillatory properties which may provide a therapeutic approach to the prevention of SCD.