LACK OF RELATIONSHIP BETWEEN OPIOID-INDUCED CHANGES IN FETAL BREATHING AND PLASMA-GLUCOSE LEVELS

The mechanisms by which opioids increase or decrease fetal breathing r emain unclear. Fetal plasma glucose is known to modulate breathing act ivity, and opioids have been reported to alter glucose regulation in t he adult. In this study, we investigated whether alterations in fetal breathing by opioids may be explained by changes in plasma glucose lev els. We compared the effects of morphine (nonselective), [D-Ala(2),N-M e-Phe(4),Gly(5)-ol]enkephalin (DAMGO, mu-selective), and [D-Pen(2),D-P en(5)]enkephalin (DPDPE, delta-selective) on fetal breathing and plasm a 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 mu g/h icv) increased plasma glucose (P = 0.001) but reduced fetal breathing (P < 0.001). In contrast, DPDP E (30 mu g/h icv) increased fetal breathing (P = 0.026) but had no eff ect on plasma glucose concentration. These data demonstrate that the a ctions of opioids on fetal glucose regulation and breathing are depend ent on dose and receptor selectivity. However, there is no relationshi p between the effects of opioids on fetal breathing and plasma glucose concentration.