Reddy VM, McElhinney DB, Rajasinghe HA, Rodriguez JL, Hanley FL
Division of Cardiothoracic Surgery, University of California, San Francisco, California
J Matern Fetal Investig. 1998 Mar;8(1):46-9.
Objective: Cytokines are associated with the systemic inflammatory response syndrome that occurs after cardiopulmonary bypass. We hypothesized that the placental dysfunction which has been found to complicate fetal cardiac bypass may be in part a function of a cytokine-mediated acute phase reaction. To test this hypothesis, we designed a study to investigate the effect of cardiac bypass on interleukin-1beta (IL-1beta), IL-6, and IL-8 in fetal sheep.Methods: Nine mixed-breed pregnant ewes at 118-122 days of gestation were assigned randomly to either the "fetal cardiac bypass group" (n = 5) or the "control group" (n = 4). After surgical exposure and instrumentation, cardiac bypass was performed for 30 min in study group fetuses, whereas control group fetuses were exposed and instrumented identically but did not undergo bypass. Placental and systemic hemodynamics were monitored in both groups. Pre- and post-bypass blood samples were analyzed for IL-1beta, IL-6, and IL-8 using enzyme-linked immunosorbent assays.Results: IL-6 levels were undetectable before bypass in all fetuses. IL-6 increased after bypass in all bypass group fetuses to 53.0 +/- 24.2 pg/ml, whereas IL-6 levels remained undetectable in all control animals. Fetal cardiac bypass produced no significant changes in IL-1beta and IL-8 in either group. Following bypass, placental blood flow decreased by 23% in the bypass group, which was significantly more (P = 0.0002) than the 6% decrease in the control group; placental vascular resistance increased significantly more in the bypass group (20%) than in control fetuses (1%; p = 0.004).Conclusions: Fetal cardiac bypass produces significant and consistent increases in fetal plasma IL-6, which correlate with increased placental vascular resistance and decreased placental blood flow. IL-6 may have an important role in placental dysfunction following fetal cardiac bypass, but further investigation will be necessary to elucidate its specific role in the impairment of placental function or as a marker of placental injury.
细胞因子与体外循环后发生的全身炎症反应综合征相关。我们推测，已发现的并发胎儿体外循环的胎盘功能障碍可能部分是细胞因子介导的急性期反应的结果。为验证这一假设，我们设计了一项研究，以调查体外循环对胎羊白细胞介素-1β（IL-1β）、IL-6和IL-8的影响。
将9只妊娠118 - 122天的杂种孕羊随机分为“胎儿体外循环组”（n = 5）或“对照组”（n = 4）。手术暴露并安装仪器后，研究组胎儿进行30分钟的体外循环，而对照组胎儿进行相同的暴露和仪器安装，但不进行体外循环。两组均监测胎盘和全身血流动力学。使用酶联免疫吸附测定法分析体外循环前后血样中的IL-1β、IL-6和IL-8。
所有胎儿在体外循环前IL-6水平均未检测到。所有体外循环组胎儿体外循环后IL-6升高至53.0±24.2 pg/ml，而所有对照动物的IL-6水平仍未检测到。胎儿体外循环对两组的IL-1β和IL-8均无显著影响。体外循环后，体外循环组胎盘血流量下降23%，显著高于对照组的6%下降幅度（P = 0.0002）；体外循环组胎盘血管阻力增加20%，显著高于对照胎儿的1%（p = 0.004）。
胎儿体外循环可使胎儿血浆IL-6显著且持续升高，这与胎盘血管阻力增加和胎盘血流量减少相关。IL-6可能在胎儿体外循环后的胎盘功能障碍中起重要作用，但需要进一步研究以阐明其在胎盘功能损害中的具体作用或作为胎盘损伤标志物的作用。
