THE PIGLET AS A SUITABLE ANIMAL-MODEL FOR STUDYING THE DELAYED PHASE OF CISPLATIN-INDUCED EMESIS

In 46 weaned piglets we surgically implanted a cannula in the jugular vein and electrodes for ECG and EMG recordings. After a 4- to 5-day re covery, piglets were hydrated, then dosed with cisplatin (5.5 mg/kg i. v.) and recorded continuously for the next 60 h. Thirteen piglets (i.e ., controls) received only cisplatin. Twenty-three other piglets recei ved, 15 min before cisplatin, an i.v. injection of granisetron (0.25, 0.5, 2 or 7 mg/kg) or ondansetron (0.5, 2 or 7 mg/kg). Ten other pigle ts received, in addition to cisplatin, multiple injections of graniset ron (1 mg/kg) and ondansetron (3.5 mg/kg). All control piglets exhibit ed both acute and delayed emesis. The first vomiting occurred with a l atency of 2.13 +/- 0.82 hr after cisplatin administration; emetic inte nsity reached a peak (5 vomits/hr) within 2 hr and then decreased rapi dly. No vomiting was observed between the 16th and 18th hr. The mean n umber of vomits during the first 16th was 18.4 +/- 2. Delayed emesis s tarted at the 18th hr and lasted until the 58th hr. The mean number of vomits during the whole of the delayed phase was 9.6 +/- 2.4; the hig hest emetic intensity (1.2 vomit/hr) occurred between the 21th and the 22th hr. Pretreatment with a 5-HT3 receptor antagonist increased sign ificantly the latency of the first emetic event in a dose-dependent ma nner. However, the severity of the acute phase was reduced significant ly only with granisetron at the dose of 7 mg/kg, although the severity of the delayed phase remained unchanged, irrespective of the dose of granisetron. Three about five piglets treated repeatedly with graniset ron did not vomit throughout the chemotherapy course. In contrast, no complete control was observed with repetitive injections of ondansetro n. Cisplatin inducing both acute and delayed vomiting in the piglet wi thout any lethality; this animal is a suitable model in which to study the pathogenesis of delayed emesis.