Lack of relationship between opioid-induced changes in fetal breathing and plasma glucose levels

Abstract

The mechanisms by which opioids increase or decrease fetal breathing remain unclear. Fetal plasma glucose is known to modulate breathing activity, and opioids have been reported to alter glucose regulation in the adult. In this study, we investigated whether alterations in fetal breathing by opioids may be explained by changes in plasma glucose levels. We compared the effects of morphine (nonselective), [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO, mu-selective), and [D-Pen2,D-Pen5]enkephalin (DPDPE, delta-selective) on fetal breathing and plasma glucose in unanesthetized fetal sheep. Whereas morphine at 1.2 and 5.0 mg/h iv resulted in an increase in breath number (P < 0.01), plasma glucose was decreased after 1.2 mg/h (P = 0.006) but increased after 5.0 mg/h (P = 0.008). DAMGO (100 micrograms/h icv) increased plasma glucose (P = 0.001) but reduced fetal breathing (P < 0.001). In contrast, DPDPE (30 micrograms/h icv) increased fetal breathing (P = 0.026) but had no effect on plasma glucose concentration. These data demonstrate that the actions of opioids on fetal glucose regulation and breathing are dependent on dose and receptor selectivity. However, there is no relationship between the effects of opioids on fetal breathing and plasma glucose concentration.