Role of the sympathetic nervous system in daunomycin-induced arrhythmia in the monkey

1. Infusion of daunomycin 50 mg/kg in the monkey consistently induced ventricular arrhythmias which were not influenced by bilateral vagotomy.2. A central sympathetic component to the arrhythmias was suggested because spinal transection, ganglionic blockade or bilateral stellate ganglionectomy prevented any alterations in the e.c.g.3. Bilateral adrenalectomy or splanchnic nerve section protected three of six animals. This source of catecholamines may not be necessary in every case to initiate the arrhythmia.4. Guanethidine was a relatively ineffective antiarrhythmic agent. Timing appears to be important with this agent.5. Pargyline, by monoamine oxidase inhibition or other mechanisms, significantly lowered the arrhythmic dose of daunomycin. Reserpine pretreatment, on the other hand, prevented any e.c.g. alterations following daunomycin.6. Phenoxybenzamine exerted significant protection which may be related to its cardiodepressant properties.7. Alterations in e.c.g. were seen in all (+)-propranolol pretreated animals, although the arrhythmic period was modified in two of three experiments. Racemic (+/-) propranolol, which exerts direct myocardium depression as well as beta-adrenoceptor blockade, was completely protective in four of five experiments. The results of the present experiments indicate that the sympathetic nervous system is intimately involved in the daunomycin arrhythmia.