Although it is widely assumed that the early arrhythmogenic and pressor responses to
bretylium are caused by
catecholamine release from the adrenergic neuron, this assumption has not been systematically studied in humans. Pharmacologic responses to a placebo infusion and 3 separate
bretylium infusions (2.5, 5.0, 10 mg/kg over 60 minutes) were assessed in 6 patients with recurrent,
nonsustained ventricular tachycardia. Plasma
bretylium concentration, blood pressure (BP), plasma
norepinephrine (NE) concentration,
arrhythmia frequency and
adrenergic neuronal blockade (assessed by the presence or absence of reflex venoconstriction) were measured.
Adrenergic blockade was seen with every
bretylium infusion and at a time when relatively small amounts of
bretylium had been administered (range 160 to 750 mg, median 252). Temporal relations (p less than 0.03) were noted among the time of onset of
adrenergic neuronal blockade, onset of the pressor response, increase in NE plasma concentration and increase in ventricular
arrhythmia frequency. BP responses during the infusions were linearly related to change in plasma NE at the time of development of
adrenergic neuronal blockade.
Bretylium plasma concentrations higher than 3 micrograms/ml were frequently associated with a short-lived pressor response. There was a significant relation (p less than 0.06) between the increase in plasma NE during the infusion and an increase in ventricular
arrhythmia frequency. Reduction in
arrhythmia frequency was seen in only 1 patient, beginning 6 hours after the development of
adrenergic neuronal blockade.(ABSTRACT TRUNCATED AT 250 WORDS)