Increases in CSF norepinephrine associated with the onset of digoxin-induced arrhythmias

The present study utilized a time course of CSF catecholamine concentrations during peripheral digoxin administration in vivo to provide a clarification of central catecholaminergic mechanisms involved in digitalis cardiotoxicity. A continuous peripheral digoxin infusion produced significant increases in CSF norepinephrine just prior to arrhythmogenesis in anesthetized dogs. Phentolamine pretreatment significantly increased the arrhythmogenic and lethal doses of digoxin. These results suggest that activation of central noradrenergic neurons may be the initiating factor in digoxin-induced arrhythmogenesis.