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

背景：此前已有胎儿体外循环引起的脐动脉内皮功能障碍的报道。本实验观察了内皮素受体阻滞剂对脐动脉内皮细胞功能和胎盘功能的影响。方法：21只胎羊随机分为对照组(C组，n=7)、泵组(P组，n=7)和泵加内皮素阻滞剂组(E组，n=7)。P组和E组采用带离心泵的低位预充循环，体外循环30min。E组在实验过程中给予内皮素-1受体阻滞剂TKA-044(3 mg/h)。泵组分别于转流前、转流中、转流后30分钟、60分钟进行血流动力学和血气分析。在转流结束60分钟后采集脐动脉。内皮依赖性松弛(缓激肽(BK)、钙离子载体(A231I87))和非内皮依赖性松弛(SO…用60 mM钾或5-羟色胺收缩血管后，测定更多硝普钠(硝普钠)，并比较两组之间的差异。结果：与C组比较，P组血管内皮依赖性舒张功能受损：BK组(60 mM K：C组；42.7±3.7%，P组；23.0±3.6%，P=0.0023；-羟色胺：C组(43.6±6.4%，P组；18.9±2.5%，P=0.0022)；A23187组(60 mM K：C组：53.8±6.9%，P组；20.9±3.6%，P组；5-羟色胺：C组；37.8±1.5%，P组；19.6±3.9%，p=0.0093)。内皮素受体阻滞剂可减轻这种损害(BK：60mK；41.6±8.6%，5-羟色胺；46.3±4.1%，A23187：60mK；37.0±8.3%，5-羟色胺；35.4±7.3%)。同时，各组均保留了非内皮依赖性的松弛。转流后30分钟和60分钟，P组和E组胎儿脐动脉血流量和主动脉压均有不同程度的下降，低氧、高碳酸血症和代谢性酸中毒的发生与血管内皮功能无关。结论：胎儿体外循环必然引起脐动脉内皮细胞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细胞功能障碍与胎盘功能障碍关系不大

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