Evaluation of pathophysiology of the fetal umbilical artery function in the fetal cardiac bypass

背景：此前，胎儿心脏搭桥引起的脐动脉内皮功能障碍已有报道。本文研究了内皮素受体阻滞剂对脐动脉内皮功能和胎盘功能的影响。方法：将21只胎羊分为对照组（C组，n=7）、泵组（P组，n=7）和内皮素受体阻滞剂泵组（E组，n=7）。P组和E组采用离心泵低启动回路维持心脏旁路30分钟。E组在实验期间给予内皮素-1受体阻滞剂TKA-044 （3 mg/h）。泵组分别在旁路术前、旁路中、旁路后30分钟和60分钟进行血流动力学测量和血气分析。停桥60分钟后切除脐动脉。在平滑肌收缩后用60mm钾或血清素测量内皮依赖性舒张（缓激肽（BK）、钙离子（A231I87））和内皮依赖性舒张（so…More dium nitroprusside），并比较两组间的差异。结果：与C组相比，P组内皮依赖性松弛被BK （60 mM K: C组；42.7±3.7%，P组；23.0±3.6%,P =0.0023； -HT: C组；43.6±6.4%，P组；18.9±2.5%,P =0.0022）或A23187 （60 mM K: C组；53.8±6.9%，P组；20.9±3.6%,P =0.0011；5-HT: C组；37.8±1.5%，P组；19.6±3.9%,P =0.0093）损害。内皮素受体阻断剂可减轻这种损害（BK:60 mK;41.6±8.6%,5-HT;46.3±4.1%,A23187:60 mK;37.0±8.3%,5-HT;35.4±7.3%）。同时，各组均保持内皮非依赖性松弛。P组和e组在搭桥后30分钟和60分钟胎儿脐动脉流量和主动脉压均明显下降，搭桥期间和搭桥后出现缺氧、高碳酸血症和代谢性酸中毒，与内皮功能无关。结论：胎儿心脏搭桥术确实引起了脐动脉内皮功能障碍和代谢性酸中毒引起的血流动力学恶化。内皮素-1受体阻滞剂可预防内皮功能障碍，但不能预防胎盘功能障碍。胎儿心脏搭桥术后脐动脉内皮功能障碍对胎盘功能障碍的影响较小

Background : Previously, endothelial dysfunction of the umbilical artery due to fetal cardiac bypass has been reported. Here, the effect ofendothelin receptor blocker on the endothelialfunction of the umbilical artery and the placental function was investigated. Methods : Twenty one fetal lambs were divided into a control group (Group C;n=7), apump group (Group P;n=7) and a pump with endothelin blocker group (Group E;n=7). In group P and group E, cardiac bypass was maintained for 30 minutes using a low priming circuit with a centrifugal pump. In group E, endothelin-1 receptor blocker, TKA-044 (3 mg/hour) was administered to the fetus during the experiment. Hemodynamic measurements and blood gas analyses were performed before, during, and 30 and 60 minutes after the bypass in the pump group. The umbilical artery was harvested 60 minutes after cessation of the bypass. Endothelium-dependent relaxation (bradykinin(BK), calcium ionophore (A231I87)) and endothelium-independent relaxation (so … More dium nitroprusside) were measured after smooth muscle contraction by 60 mM potassium or serotonin and compared between the two groups. Results : Endothelium-dependent relaxation was impaired in group P compared with group C either by BK (60 mM K : group C;42.7±3.7%, group P;23.0±3.6%, p=0.0023; -HT : group C;43.6±6.4%, group P;18.9±2.5%, p=0.0022) or by A23187 (60 mM K:group C;53.8±6.9%, group P;20.9±3.6%, p=0.0011;5-HT : group C;37.8±1.5%, group P;19.6±3.9%, p=0.0093). Endothelin receptor blocker attenuated this impairment (BK:60 mK;41.6±8.6%,5-HT;46.3±4.1%, A23187:60 mK;37.0±8.3%,5-HT;35.4±7.3%). Meanwhile, endothelium-independent relaxation was preserved in all groups. The umbilical artery flow and aortic pressure of the fetus were similarly decreased at 30 and 60 minutes after the bypass in group P and group E.Hypoxia, hypercapnia and metabolic acidosis progressed during and after the bypass independent of endothelialfunction. Conclusions : Fetal cardiac bypass certainly caused endothelial dysfunction of the umbilical artery and hemodynamic deterioration due to metabolic acidosis. Endothelin-1 receptor blocker prevented endothelial dysfunction but not placental dysfunction. Endothelial dysfunction of the umbilical artery afterfetal cardiac bypass did not play an important role of placental dysfunction Less