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

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Abstract
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 ganglion-ectomy 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 pre-treatment, 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 β-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.