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

Abstract

Infusion of daunomycin 50 mg/kg in the monkey consistently induced ventricular arrhythmias which were not influenced by bilateral vagotomy. 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. 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. Guanethidine was a relatively ineffective antiarrhythmic agent. Timing appears to be important with this agent. 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. Phenoxybenzamine exerted significant protection which may be related to its cardiodepressant properties. 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.

Daunomycin (Daunorubicin) and Adriamycin and Structural Analogues: Biological Activity and Mechanism of Action

“…As it can be expected for drugs which interfere with nucleic acids synthesis, the tissues most susceptible to the two antibiotics are rapidly proliferating such as intestinal mucosa, lymphoid organs and bone marrow. Few signs of cardiac toxicity have been seen in experimental animals; some EKG alterations have been observed in the hamster (HER-MAN et al, 1969;HERMAN et aI., 1970) and in the monkey (BURKA et al, 1970) possibly mediated by a central mechanism involving the sympathetic nervous system (BURKA et al, 1970;HERMAN et aI., 1970).…”