Reddy V M, McElhinney D B, Rajasinghe H A, Liddicoat J R, Hendricks-Munoz K, Fineman J R, Hanley F L
Division of Cardiothoracic Surgery, University of California-San Francisco, USA.
J Thorac Cardiovasc Surg. 1999 Feb;117(2):343-51. doi: 10.1016/S0022-5223(99)70432-0.
Fetal cardiac bypass causes placental dysfunction, characterized by increased placental vascular resistance, decreased placental blood flow, hypoxia, and acidosis. Vasoactive factors produced by the vascular endothelium, such as nitric oxide and endothelin 1, are important regulators of placental vascular tone and may contribute to this placental dysfunction.
To investigate the role of the vascular endothelium in placental dysfunction related to fetal cardiac bypass, we studied 3 groups of fetal sheep. In the first group (n = 7) we determined placental hemodynamic responses before and after bypass to an endothelium-dependent vasodilator (acetylcholine), an endothelium-independent vasodilator (nitroprusside), and endothelin 1. In the second group (n = 8) a nonspecific endothelin receptor blocker (PD 145065) was administered and placental hemodynamic values were measured before and after bypass. In the third group (n = 5) endothelin 1 levels were measured before and after bypass.
Before fetal cardiac bypass exogenous endothelin 1 decreased placental blood flow by 9% and increased placental resistance by 9%. After bypass endothelin 1 decreased placental flow by 47% and increased resistance by 106%. There was also a significant attenuation of the placental vascular relaxation response to acetylcholine after bypass, whereas the response to nitroprusside was not significantly altered. In fetuses that received the PD 145065, placental vascular resistance increased significantly less than in control fetuses (28% versus 62%). Similarly, placental blood flow decreased significantly more (from 6. 3 +/- 3.1 to 28.3 +/- 10.4 pg/mL; P =.01) in control fetuses than in fetuses receiving PD 145065 (33% versus 20%). Umbilical venous endothelin 1 levels increased significantly in fetuses exposed to fetal bypass but did not change in control fetuses.
The basal endothelial regulatory mechanisms of placental vascular tone were deranged after fetal cardiac bypass. Endothelin receptor blockade, which substantially reduced postbypass placental dysfunction, and other interventions aimed at preserving endothelial function may be effective means of optimizing fetal outcome after cardiac bypass.
胎儿体外循环会导致胎盘功能障碍，其特征为胎盘血管阻力增加、胎盘血流量减少、缺氧及酸中毒。血管内皮产生的血管活性因子，如一氧化氮和内皮素-1，是胎盘血管张力的重要调节因子，可能导致这种胎盘功能障碍。
为研究血管内皮在与胎儿体外循环相关的胎盘功能障碍中的作用，我们对三组胎羊进行了研究。在第一组（n = 7）中，我们测定了体外循环前后胎盘对内皮依赖性血管扩张剂（乙酰胆碱）、非内皮依赖性血管扩张剂（硝普钠）和内皮素-1的血流动力学反应。在第二组（n = 8）中，给予非特异性内皮素受体阻滞剂（PD 145065），并在体外循环前后测量胎盘血流动力学值。在第三组（n = 5）中，测量体外循环前后内皮素-1水平。
在胎儿体外循环前，外源性内皮素-1使胎盘血流量减少9%，胎盘阻力增加9%。体外循环后，内皮素-1使胎盘血流量减少47%，阻力增加106%。体外循环后胎盘对乙酰胆碱的血管舒张反应也显著减弱，而对硝普钠的反应无明显改变。在接受PD 145065的胎儿中，胎盘血管阻力的增加明显低于对照胎儿（28%对62%）。同样，对照胎儿的胎盘血流量减少幅度明显大于接受PD 145065的胎儿（从6.3±3.1降至28.3±10.4 pg/mL；P =.01）（33%对20%）。暴露于胎儿体外循环的胎儿脐静脉内皮素-1水平显著升高，而对照胎儿则无变化。
胎儿体外循环后胎盘血管张力的基础内皮调节机制紊乱。内皮素受体阻滞可显著减轻体外循环后胎盘功能障碍，其他旨在保护内皮功能的干预措施可能是优化体外循环后胎儿结局的有效手段。
