Ketamine inhibits fetal reflex response to cerebral hypoperfusion

Abstract

Fetal sheep respond to hypoxia, hypotension and hypovolemia with reflex increases in circulating concentrations of adrenocorticotropin (ACTH) and cortisol. Previous studies indicate that these reflex responses may be more dependent on afferent activity of arterial chemoreceptors than baroreceptors. This suggests that these responses will be vulnerable to drugs that inhibit the fetal chemoreflex. Ketamine, a dissociative anesthetic that blocks the fetal reflex response to maternal ventilatory hypoxia, may act in this manner. We hypothesized that ketamine would block the reflex ACTH, pro-opiomelanocortin (POMC), and cortisol response to brachiocephalic occlusion (BCO), a stimulus that mimics the reduction in cerebral blood flow that results from severe fetal hypotension. Chronically catheterized fetal sheep (125–135 days gestation) were subjected to 10 minutes of cerebral hypoperfusion induced by occlusion of the brachiocephalic artery with or without pretreatment with iv ketamine (3mg/kg). Fetal blood samples were assayed for plasma ACTH, POMC, and cortisol. BCO stimulated robust increases in plasma ACTH and POMC levels that were significantly inhibited in ketamine-treated fetuses. Plasma cortisol was also significantly increased by occlusion; however, this rise was not attenuated by ketamine. We conclude that ketamine does block fetal reflex ACTH and POMC but not cortisol response to BCO. These data agree with our previous results demonstrating that sinoaortic denervation of chemoreceptors and baroreceptors prior to occlusion attenuates fetal ACTH stimulation and suggests that ketamine may inhibit chemoreflex and/or baroreflex pathways. Supported by HD42135 and an AHA pre-doctoral fellowship.