Jellyman J K, Gardner D S, Edwards C M B, Fowden A L, Giussani D A
The Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
J Physiol. 2005 Sep 1;567(Pt 2):673-88. doi: 10.1113/jphysiol.2005.089805. Epub 2005 Jun 23.
In sheep, direct fetal treatment with dexamethasone alters basal cardiovascular function and the cardiovascular response to acute hypoxaemia. However, in human clinical practice, dexamethasone is administered to the mother, not to the fetus. Hence, this study investigated physiological responses to acute hypoxaemia in fetal sheep during and following maternal treatment with dexamethasone in doses and at dose intervals used in human clinical practice. Under anaesthesia, 18 fetal sheep were instrumented with vascular and amniotic catheters, a carotid flow probe and a femoral flow probe at 118 days gestation (term ca 145 days). Following 6 days recovery at 124 days gestation, 10 ewes received dexamethasone (2 x 12 mg daily i.m. injections in saline). The remaining animals were saline-injected as age-matched controls. Two episodes of hypoxaemia (H) were induced in all animals by reducing the maternal F(IO2)for 1 h (H1, 8 h after the second injection; H2, 3 days after the second injection). In fetuses whose mothers received saline, hypoxaemia induced significant increases in fetal arterial blood pressure, carotid blood flow and carotid vascular conductance and femoral vascular resistance, significant falls in femoral blood flow and femoral vascular conductance and transient bradycardia. These cardiovascular responses were accompanied by a fall in arterial pH, increases in blood glucose and blood lactate concentrations and increased plasma concentrations of catecholamines. In fetuses whose mothers were treated with dexamethasone, bradycardia persisted throughout hypoxaemia, the magnitude of the femoral vasoconstriction, the glycaemic, lactacidaemic and acidaemic responses and the plasma concentration of neuropeptide Y (NPY) were all enhanced during H1. However, during H2, all of these physiological responses were similar to saline controls. In dexamethasone fetuses, the increase in plasma adrenaline was attenuated during H1 and the increase in carotid vascular conductance during hypoxaemia failed to reach statistical significance both during H1 and during H2. These data show that maternal treatment with dexamethasone in doses and intervals used in human obstetric practice modified the fetal cardiovascular, metabolic and endocrine defence responses to acute hypoxaemia. Furthermore, dexamethasone-induced alterations to these defences depended on whether the hypoxaemic challenge occurred during or following maternal dexamethasone treatment.
在绵羊中，用地塞米松直接对胎儿进行治疗会改变基础心血管功能以及对急性低氧血症的心血管反应。然而，在人类临床实践中，地塞米松是给予母亲而非胎儿。因此，本研究调查了在人类临床实践中使用的剂量和剂量间隔下，母亲接受地塞米松治疗期间及之后，胎羊对急性低氧血症的生理反应。在麻醉状态下，于妊娠118天（足月约145天）时，对18只胎羊植入血管和羊膜导管、颈动脉血流探头和股动脉血流探头。在妊娠124天恢复6天后，10只母羊接受地塞米松治疗（每日2次，每次12毫克，肌肉注射于生理盐水中）。其余动物注射生理盐水作为年龄匹配的对照。通过降低母体吸入氧分数（F(IO2)）1小时，在所有动物中诱导两次低氧血症发作（H）（H1，第二次注射后8小时；H2，第二次注射后3天）。在母亲接受生理盐水注射的胎儿中，低氧血症导致胎羊动脉血压、颈动脉血流和颈动脉血管传导性显著增加，股血管阻力显著增加，股血流和股血管传导性显著下降以及短暂性心动过缓。这些心血管反应伴随着动脉pH值下降、血糖和血乳酸浓度升高以及血浆儿茶酚胺浓度增加。在母亲接受地塞米松治疗的胎儿中，心动过缓在整个低氧血症期间持续存在，在H1期间，股血管收缩幅度、血糖、血乳酸和酸血症反应以及神经肽Y（NPY）的血浆浓度均增强。然而，在H2期间，所有这些生理反应与生理盐水对照组相似。在地塞米松治疗的胎儿中，H1期间血浆肾上腺素的增加减弱，低氧血症期间颈动脉血管传导性的增加在H1和H2期间均未达到统计学显著性。这些数据表明，以人类产科实践中使用的剂量和间隔对母亲进行地塞米松治疗，会改变胎儿对急性低氧血症的心血管、代谢和内分泌防御反应。此外，地塞米松对这些防御的诱导性改变取决于低氧血症挑战发生在母亲地塞米松治疗期间还是之后。
