Intravenous infusion of cyclopentenyl-cytosine (CPE-C) in the canine markedly inhibits the response to bilateral carotid occlusion

Use of the candidate antineoplastic agent CPE-C is sometimes associated with orthostatic hypotension. In some patients, no reflex increase in heart rate occurs. We have attempted to determine if this is due to a CPE-C-induced diminution in the carotid baroreceptor reflex. We measured mean systemic, systolic, diastolic, pulse and central venous pressures and heart rate while clamping both carotid arteries every 30 minutes for two control periods during a four hour CPE-C infusion. In control experiments, the response to bilateral carotid occlusion (BCO) was well maintained. In animals receiving CPE-C (75 mg/kg i.v.), the response to BCO was markedly inhibited by minute 180 of the infusion period. In animals which were followed an additional two hours after cessation of CPE-C, the response to BCO continued to decline. To determine if the antiemetic agent Zofran, which is usually given to patients prior to CPE-C, also caused a diminution in the response to BCO, we gave Zofran over a 15 minute period (15 mg/kg, i.v.) followed by a 4 hour infusion of CPE-C. In these experiments, not only was the response to BCO unaffected by the Zofran alone, but subsequent CPE-C also no longer attenuated the response. The protection of the BCO response by the serotonin antagonist Zofran suggests that CPE-C may attenuate the carotid baroreceptor reflex in these animals through mechanisms which include central serotonin receptors.