Fletcher Andrew J W, McGarrigle Hugh H G, Edwards C Mark B, Fowden Abigail L, Giussani Dino A
Department of Physiology, University of Cambridge, Cambridge CB2 3EG, UK.
J Physiol. 2002 Dec 1;545(2):649-60. doi: 10.1113/jphysiol.2001.015693.
This study investigated the effects on ovine fetal basal cardiovascular and endocrine functions of fetal intravenous dexamethasone treatment, resulting in circulating concentrations that were one-fifth of the values measured clinically in human infants following maternal antenatal glucocorticoid therapy. Between 117-120 days gestation (dGA; term: ca 145 dGA), 26 Welsh Mountain sheep fetuses were surgically prepared under general anaesthesia with vascular catheters and a Transonic flow probe positioned around a femoral artery. At 125 +/- 1 dGA, fetuses were infused with dexamethasone (2.06 +/- 0.13 microg kg(-1) h(-1) i.v.; n = 13) or saline (n = 13) for 48 h. Daily fetal arterial blood samples were taken and cardiovascular data were recorded continuously (data acquisition system). Pressor, vasoconstrictor and chronotropic responses to exogenously administered doses of phenylephrine, angiotensin II and arginine vasopressin (AVP) were determined at 124 +/- 1 (pre-infusion), 126 +/- 1 (during infusion) and 128 +/- 1 (post-infusion) dGA. Fetal cardiac baroreflex curves were constructed using peak pressor and heart rate responses to phenylephrine. Dexamethasone treatment elevated fetal mean arterial blood pressure by 8.1 +/- 1.0 mmHg (P < 0.05), increased femoral vascular resistance by 0.65 +/- 0.12 mmHg (ml min(-1))(-1) (P < 0.05), depressed plasma noradrenaline concentrations and produced a shift in set-point, but not sensitivity, of the cardiac baroreflex (P < 0.05). Elevations in fetal arterial blood pressure, but not femoral vascular resistance and the shift in baroreflex set-point, persisted at 48 h following dexamethasone treatment. By 48 h following dexamethasone infusion, basal plasma noradrenaline concentration was restored, whilst plasma adrenaline and neuropeptide Y (NPY) concentrations were enhanced, compared with controls (P < 0.05). Fetal dexamethasone treatment did not alter the fetal pressor or femoral vasoconstrictor responses to adrenergic, vasopressinergic or angiotensinergic agonists. These data show that fetal treatment with low concentrations of dexamethasone modifies fetal basal cardiovascular and endocrine functions. Depending on the variable measured, these changes may reverse, persist or become enhanced by 48 h following the cessation of treatment.
本研究调查了胎儿静脉注射地塞米松治疗对绵羊胎儿基础心血管和内分泌功能的影响，所产生的循环浓度是人类婴儿在母体产前糖皮质激素治疗后临床测量值的五分之一。在妊娠117 - 120天（妊娠天数，dGA；足月：约145 dGA）时，对26只威尔士山地绵羊胎儿在全身麻醉下进行手术，植入血管导管，并在股动脉周围放置Transonic血流探头。在125±1 dGA时，给胎儿输注地塞米松（2.06±0.13微克·千克⁻¹·小时⁻¹，静脉注射；n = 13）或生理盐水（n = 13），持续48小时。每天采集胎儿动脉血样本，并连续记录心血管数据（数据采集系统）。在124±1（输注前）、126±1（输注期间）和128±1（输注后）dGA时，测定对外源性给予的去氧肾上腺素、血管紧张素II和精氨酸加压素（AVP）剂量的升压、血管收缩和变时反应。使用对去氧肾上腺素的峰值升压和心率反应构建胎儿心脏压力反射曲线。地塞米松治疗使胎儿平均动脉血压升高8.1±1.0 mmHg（P < 0.05），股血管阻力增加0.65±0.12 mmHg·（毫升·分钟⁻¹）⁻¹（P < 0.05），降低血浆去甲肾上腺素浓度，并使心脏压力反射的设定点发生偏移，但不影响其敏感性（P < 0.05）。地塞米松治疗后48小时，胎儿动脉血压升高持续存在，但股血管阻力和压力反射设定点的偏移未持续。与对照组相比，在地塞米松输注后48小时，基础血浆去甲肾上腺素浓度恢复，而血浆肾上腺素和神经肽Y（NPY）浓度升高（P < 0.05）。胎儿地塞米松治疗未改变胎儿对肾上腺素能、加压素能或血管紧张素能激动剂的升压或股血管收缩反应。这些数据表明，低浓度地塞米松对胎儿的治疗会改变胎儿基础心血管和内分泌功能。根据所测量的变量，这些变化在治疗停止后48小时可能会逆转、持续或增强。
