Naloxone potentiates the plasma catecholamine response to asphyxia in the fetus.

The effect of endogenous opioid peptide blockade with naloxone on the plasma catecholamine response to asphyxia (hypoxemia + acidemia) was investigated in 6 chronically catheterized late gestation (greater than or equal to 120 days) fetal lambs in utero. Animals were assigned randomly to receive either naloxone (1 mg/kg) or saline on alternate days. Hypoxemia was produced by gradual umbilical cord compression until arterial PO2 less than 15 Torr and maintained for 15 min. This resulted in the development of acidemia as pH decreased from a baseline of 7.41 +/- 0.02 to 7.25 +/- 0.01. Fetal heart rate declined initially from 183 +/- 5 to 113 +/- 7 beats/min and then increased progressively to approach, but not return, to baseline, whereas mean arterial pressure continued to rise from 45 +/- 2 Torr throughout the 15-min observation period to a peak of 61 +/- 5 Torr. No difference was noted between control and naloxone-treated fetuses in their blood pH, PO2, PCO, heart rate or blood pressure responses to asphyxia. Plasma epinephrine concentrations increased 10-fold from 143 +/- 45 to 1391 +/- 290 pg/ml in control fetuses and from 254 +/- 58 to 6944 +/- 847 pg/ml, a 27-fold increase, in naloxone-treated fetuses (p less than 0.05). Norepinephrine levels were not significantly altered by opioid receptor blockade, increasing from 525 +/- 121 to 4138 +/- 912 pg/ml in controls and from 719 +/- 186 to 6,958 +/- 1,439 pg/ml in naloxone-treated animals. Thus, naloxone potentiates the plasma epinephrine response to asphyxia. Endogenous opioid peptides may act as modulators of the sympathoadrenal response to severe stress in the fetus.