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Latex-induced transmural myocardial infarction or epicardial application of phenol interrupts sympathetic fibers innervating myocardium apical to the infarction or to the phenol-painted area. These denervated regions subsequently show supersensitive shortening of effective refractory period (ERP) in response to the infusion of norepinephrine (denervation supersensitivity). The purpose of this study was to test the hypothesis that such denervation supersensitivity is arrhythmogenic. Ventricular arrhythmias were elicited by programmed ventricular stimulation (PVS) during a control period, during bilateral stimulation of the ansae subclaviae (4 msec pulses, 4 Hz and 3 mA), and during the infusion of norepinephrine (0.5 microgram/kg/min). Study groups consisted of 14 sham-operated dogs, 16 dogs with phenol painted over a diagonal branch, 13 dogs with latex embolization of a diagonal branch that resulted in transmural myocardial infarction, 14 dogs with a one-stage ligation of a diagonal branch producing nontransmural myocardial infarction, and 12 dogs undergoing both phenol painting and one-stage ligation of a diagonal branch. Four to 22 days after the first operation, PVS was performed in anesthetized, open-chest dogs after neural decentralization of the heart. Dogs with phenol painting on the epicardium and dogs in which latex was injected into a diagonal branch showed supersensitive shortening of ERP to infused norepinephrine at apical sites. PVS resulted in ventricular fibrillation more often during stimulation of the ansae subclaviae (p less than .001) and infusion of norepinephrine (p less than .001) than during the control state in dogs treated with phenol alone. The incidence of ventricular fibrillation was highest in dogs with ligation-induced infarction that received phenol compared with all other groups during control (p less than .001), stimulation of the ansae subclaviae (p less than .002), and the infusion of norepinephrine (p less than .01). Propranolol (0.5 mg/kg or 10 mg iv at maximum) attenuated supersensitive shortening of ERP and decreased the incidence of induction of ventricular fibrillation.(ABSTRACT TRUNCATED AT 400 WORDS)