Establishment of Fetal Extra-corporeal circulation for Fetal Cardiac Surgery : Elucidation of Pathophysiology of Fetal Circulation and Placental Function by Oxidative Stress

目的：胎儿体外循环引起的内皮功能障碍可能在胎儿心脏外科手术的建立中起重要作用。本研究采用可靠的方法探讨胎儿体外循环后脐动脉内皮功能的变化。方法：对14只胎羊进行了这项研究。将胎仔分为2组;对照组（n=7）和泵组（n=7）。泵组采用离心泵建立体外循环30 min。在体外循环前、中、后每30分钟进行血流动力学测量和血气分析。停循环后60分钟取脐动脉，用5-羟色胺收缩平滑肌，检测血管内皮依赖性舒张（缓激肽（BK）、钙离子载体（A23187））和非内皮依赖性舒张（硝普钠（SNP））。结果：体外循环后30分钟和60分钟脐动脉血流量和主动脉压明显降低。体外循环后出现低氧血症和高碳酸血症。代谢性酸中毒在皮质外循环期间和之后进展。与对照组相比，泵组的内皮依赖性舒张功能受损（BK：对照组43.6±6.4%，泵组18.9±2.5%，p<0.01; A23187：对照组37.8±4.6%，泵组19.6±3.9%，p<0.01）。同时，两组均保持了内皮非依赖性舒张功能。结论：胎儿皮质外循环确实引起了代谢性酸中毒引起的脐动脉内皮损伤和血流动力学恶化。预防内皮损伤和代谢性酸中毒可能是胎儿心脏手术成功的主要目标。

Objective : Endothelial dysfunction due to fetal extra-corporeal circulation may have an important role in, establishment of feral cardiac surgery. This study investigates the endothelial function of umbilical artery after fetal extra-corporeal circulation by reliable method. Methods : This study was undertaken in 14 fetal lambs. Fetuses were, divided into 2 groups; control group (n=7) and pump group (n=7). In pump group, extra-corporeal circulation was established for 30 minutes by centrifugal pump. Hemodynamic measurements and blood gas analysis were performed pre, during, and every 30 minutes after extra-corporeal circulation. Umbilical artery was harvested 60 minutes after cessation' of extra-corporeal circulation, and endothelium-dependent relaxation (bradykinin (BK), calcium ionophore (A23187)) and endothelium-independent relaxation (sodium nitroprusside (SNP)) were exmined after smooth muscle contraction by serotonin. Results : Umbilical artery flow and aortic pressure were significantly decreased 30 and 60 minutes after extra-corporeal circulation. Hypoxia and hypercapnia were recognized after extra-corporeal circulation. Metabolic acidosis progressed during and after extra-corporeal circulation. Endothelium-dependent relaxation was impaired in pump group compared with control group (BK: 43.6±6.4% in control group, 18.9±2.5% in pump group, p<0.01, A23187: 37.8±4.6% in control group, 19.6±3.9% in pump group, p<0.01). Meanwhile, endothelium-independent relaxation was preserved, in both groups. Conclusions : Fetal extra-corporeal circulation certainly caused endothelial impairment of umbilical artery and hemodynamic deterioration due to metabolic acidosis. Prevention of endothelial damage and metabolic acidosis could be the main target to success fetal cardiac surgery.