Julian Colleen Glyde, Galan Henry L, Wilson Megan J, Desilva Wendy, Cioffi-Ragan Darleen, Schwartz Joel, Moore Lorna G
Altitude Research Center, Dept. of Surgery, Division of Emergency Medicine, Univ. of Colorado Denver, 12469 East 17th Place, Bldg. 400, Aurora, Colorado 80045, USA.
Am J Physiol Regul Integr Comp Physiol. 2008 Sep;295(3):R906-15. doi: 10.1152/ajpregu.00164.2008. Epub 2008 Jun 25.
Reduced uteroplacental blood flow is hypothesized to play a key role in altitude-associated fetal growth restriction. It is unknown whether reduced blood flow is a cause or consequence of reduced fetal size. We asked whether determinants of uteroplacental blood flow were altered prior to reduced fetal growth and whether vasoactive and/or angiogenic factors were involved. Women residing at low (LA; 1,600 m, n = 18) or high altitude (HA; 3,100 m, n = 25) were studied during pregnancy (20, 30, and 36 wk) and 4 mo postpartum (PP) using Doppler ultrasound. In each study, endothelin (ET-1), nitric oxide metabolites (NO(x)), soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PlGF) levels were quantified. At HA, birth weights were lower (P < 0.01) and small-for-gestational age was more common (P < 0.05) compared with LA. HA was associated with lower uterine artery (UA) diameter (P < 0.01) and blood flow (P < 0.05). Altitude did not affect ET-1, sFlt-1 or PlGF; however, ET-1/NO(x) was greater and NO(x) lower during pregnancy and PP at HA vs. LA. ET-1/NO(x) was negatively associated with birth weight (20 wk, P < 0.01; 36 wk, P = 0.05) at LA and HA combined. At HA, UA blood flow (30 wk) was positively associated with birth weight (dagger). UA blood flow and ET-1/NO(x) levels accounted for 45% (20 wk) and 32% (30 wk) of birth weight variation at LA and HA combined, primarily attributed to effects at HA. We concluded that elevated ET-1/NO(x) and altered determinants of uteroplacental blood flow occur prior to altitude-associated reductions in fetal growth, and therefore, they are likely a cause rather than a consequence of smaller fetal size.
子宫胎盘血流量减少被认为在高原相关的胎儿生长受限中起关键作用。目前尚不清楚血流量减少是胎儿体型减小的原因还是结果。我们研究了在胎儿生长减缓之前子宫胎盘血流量的决定因素是否发生改变，以及血管活性和/或血管生成因子是否参与其中。在孕期（20、30和36周）以及产后4个月（PP），使用多普勒超声对居住在低海拔（LA；1600米，n = 18）或高海拔（HA；3100米，n = 25）的女性进行了研究。在每项研究中，对内皮素（ET-1）、一氧化氮代谢产物（NO(x)）、可溶性fms样酪氨酸激酶（sFlt-1）和胎盘生长因子（PlGF）水平进行了定量分析。与LA相比，HA组出生体重较低（P < 0.01），小于胎龄儿更为常见（P < 0.05）。HA与子宫动脉（UA）直径较小（P < 0.01）和血流量较低（P < 0.05）相关。海拔高度对ET-1、sFlt-1或PlGF没有影响；然而，与LA相比，HA组在孕期和产后ET-1/NO(x)更高，而NO(x)更低。在LA和HA合并组中，ET-1/NO(x)与出生体重呈负相关（20周，P < 0.01；36周，P = 0.05）。在HA组，UA血流量（30周）与出生体重呈正相关（†）。在LA和HA合并组中，UA血流量和ET-1/NO(x)水平分别解释了出生体重变异的45%（20周）和32%（30周），主要归因于HA组的影响。我们得出结论，在与高原相关的胎儿生长减少之前，ET-1/NO(x)升高以及子宫胎盘血流量的决定因素发生改变，因此，它们可能是胎儿体型较小的原因而非结果。
