CISPLATIN-INDUCED AUTONOMIC NEUROPATHY - DOES IT REALLY EXIST

The neurotoxic side-effects of cisplatin affect predominantly the larg e, myelinated fibres of peripheral nerves, leading to a sensory neurop athy Several reports of cisplatin-associated autonomic neuropathy have been published. Autonomic dysfunction however, is caused by a neuropa thy of small unmyelinated nerve fibres. By using the absolute pupil di ameter as a parameter of autonomic nervous system function, we studied autonomic neuropathy in the eye of cisplatin-intoxicated rats. In add ition, we examined autonomic cardiovascular function by measuring the change in heart rate (HR) and mean arterial blood pressure (MAP) in re sponse to intravenous phenylephrine (PHE) and tyramine (TYR). No signi ficant differences in mean pupil diameter developed in cisplatin-intox icated rats (n = 12) in the course of 9 weeks (total cumulative dose c isplatin 18 mg/kg) compared with normal controls (n = 9) (MANOVA, F-1, F-19 = 0.88, P < 0.36). The PHE- and TYR-induced changes in MAP and HR were virtually the same in cisplatin-intoxicated rats when compared w ith normal controls. We conclude that cisplatin probably does not caus e autonomic dysfunction, at least not in rats, in doses commonly used and which are known to cause a peripheral, sensory neuropathy.