Restriction of placental growth results in greater hypotensive response to α-adrenergic blockade in fetal sheep during late gestation
Restriction of placental growth results in greater hypotensive response to α-adrenergic blockade in fetal sheep during late gestation
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DOI：
10.1113/jphysiol.2004.080523
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发表时间：
2005-03-01
影响因子：
5.5
通讯作者：
Morrison, JL
中科院分区：
文献类型：
--
作者：
Danielson, L;McMillen, IC;Morrison, JL
胎盘功能不全导致胎儿基质供应限制和胎儿低氧血症是胎儿生长受限和新生儿发病率增加的主要原因。胎儿对胎盘限制（PR）的适应包括循环儿茶酚胺和皮质醇的增加以及胎儿身体生长的减少，而大脑的生长相对较少。 PR 胎儿中胎儿心输出量重新分布的机制尚不清楚，本研究的目的是确定 PR 胎儿中胎儿血压 (BP) 的维持是否依赖于 α-肾上腺素能刺激。 PR是通过在受孕前去除母羊的大部分子宫肉阜而诱导的。对妊娠 113-120 天（足月 = 150 +/- 3 天）的 7 个 PR 胎儿和 6 个对照胎儿进行了无菌血管手术。妊娠 123 至 127 天期间平均动脉 P-O2 < 17 mmHg 的胎儿被定义为缺氧。与常氧对照组（-5 +/- 1 mmHg）相比，低氧 PR 组（-15 +/- 2 mmHg）在酚妥拉明输注期间（静脉注射：5 mg 推注，0.2 mg kg(-1) min(-1)，持续 2 小时）胎儿血压下降幅度更大 (P < 0.05)。酚妥拉明输注期间胎儿血压的下降与胎儿 P-O2 水平直接相关，PR 胎儿和对照胎儿对去氧肾上腺素（静脉注射：40 μg kg(-1)）的胎儿血压和 HR 反应没有差异。因此，长期缺氧胎儿血压的维持依赖于α-肾上腺素能的激活，并且胎儿对次优宫内环境的适应早于显着生长受限的发展。虽然这种适应可能在胎儿心输出量的重新分配以确保大脑生长不受损害方面发挥关键作用，但它可能对新生儿期和成年期的外周血管功能产生不利影响。
Placental insufficiency resulting in restriction of fetal substrate supply and fetal hypoxaemia is a major cause of restricted fetal growth and increased neonatal morbidity. Fetal adaptations to placental restriction (PR) include increases in circulating catecholamines and cortisol and decreased fetal body growth, with relative sparing of brain growth. The mechanisms underlying the redistribution of fetal cardiac output in PR fetuses are not known and the aim of this study was to determine whether maintenance of fetal blood pressure (BP) in the PR fetus is dependent on alpha-adrenergic stimulation. PR was induced by removing the majority of uterine caruncles in the ewe before conception. Sterile vascular surgery was performed on seven PR and six control fetuses at 113-120 days' gestation (term = 150 +/- 3 days). Fetuses with a mean arterial P-O2 < 17 mmHg between 123 and 127 days' gestation were defined as hypoxic. There was a greater fall (P < 0.05) in fetal BP during phentolamine infusion (I.V: 5 mg bolus, 0.2 mg kg(-1) min(-1) for 2 h) in the hypoxic PR group (-15 +/- 2 mmHg) compared with normoxic controls (-5 +/- 1 mmHg). The fall in fetal BP during phentolamine infusion was directly related to the level of fetal P-O2, Fetal BP and HR responses to phenylephrine (i.v.: 40 mu g kg(-1)) were not different between PR and control fetuses. The maintenance of BP in the chronically hypoxic fetus is therefore dependent on a-adrenergic activation, and this fetal adaptation to a suboptimal intrauterine environment pre-dates the development of significant growth restriction. While this adaptation may play a critical role in the redistribution of fetal cardiac output to ensure the sparing of brain growth, it may have adverse consequences for peripheral vascular function in the neonatal period and in adult life.