Lewis A B, Sadeghi M
Division of Cardiology, Children's Hospital of Los Angeles, Calif.
Dev Pharmacol Ther. 1988;11(4):219-25. doi: 10.1159/000457692.
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.
在6只妊娠晚期（大于或等于120天）、已长期植入导管的子宫内胎羊中，研究了用纳洛酮阻断内源性阿片肽对血浆儿茶酚胺对窒息（低氧血症+酸血症）反应的影响。动物被随机分配，隔天接受纳洛酮（1毫克/千克）或生理盐水。通过逐渐压迫脐带产生低氧血症，直到动脉血氧分压低于15托，并维持15分钟。这导致酸血症的发生，pH值从基线7.41±0.02降至7.25±0.01。胎心率最初从183±5次/分钟降至113±7次/分钟，然后逐渐上升，接近但未恢复到基线水平，而平均动脉压在整个15分钟的观察期内从45±2托持续上升至61±5托的峰值。在血液pH值、血氧分压、二氧化碳分压、心率或血压对窒息的反应方面，对照组和经纳洛酮治疗的胎儿之间未发现差异。对照组胎儿血浆肾上腺素浓度从143±45皮克/毫升增加10倍至1391±290皮克/毫升，经纳洛酮治疗的胎儿从254±58皮克/毫升增加27倍至6944±847皮克/毫升（p<0.05）。阿片受体阻断对去甲肾上腺素水平无显著影响，对照组从525±121皮克/毫升增加至4138±912皮克/毫升，经纳洛酮治疗的动物从719±186皮克/毫升增加至6958±1439皮克/毫升。因此，纳洛酮增强了血浆肾上腺素对窒息的反应。内源性阿片肽可能是胎儿对严重应激的交感肾上腺反应的调节剂。
