Altered cerebrovascular responses after exposure to venoarterial extracorporeal membrane oxygenation: Role of the nitric oxide pathway
Altered cerebrovascular responses after exposure to venoarterial extracorporeal membrane oxygenation: Role of the nitric oxide pathway
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DOI：
10.1097/01.pcc.0000225372.38460.12
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发表时间：
2006-07-01
影响因子：
4.1
通讯作者：
Short, Billie L.
中科院分区：
文献类型：
--
作者：
Ingyinn, Ma;Rais-Bahrami, Khodayar;Short, Billie L.
背景：我们实验室之前对新生羔羊的研究表明，暴露于静脉动脉体外膜氧合 (VA ECMO) 后，脑血管自动调节受损，另外的研究表明，在同一模型中，羔羊脑血管对 NG-硝基-L-精氨酸甲酯的脑血管反应发生了改变。目的：进一步研究暴露于 VA ECMO 的血管中脑血管反应改变的机制。设计：前瞻性研究。设置：研究动物设施华盛顿特区儿童国家医疗中心。受试者：新生羔羊，1-7 天龄，4.76 +/- 0.8 kg（n = 10）。方法：将动物随机分配两组，对照组和 VA ECMO，麻醉、通气、肝素化并保持正常生理状态。对照组动物继续接受通气支持，而 VA ECMO 组的动物则置于 VA ECMO 上，旁路流量维持在 120 至 200 mL.kg(-1).min(-1) 之间，持续 2.5 小时。研究了大脑中动脉孤立的三级分支对增加的管腔内压力变化的肌强直反应性、对乙酰胆碱（一种内皮依赖性血管扩张剂）、3-吗啉基-悉尼亚胺氯化物（一种内皮依赖性血管扩张剂）和血清素（一种直接血管收缩剂）的反应。使用视频显微镜监测动脉管径。结果：与对照组相比，VA ECMO 组的肌源性收缩反应显着降低 (p = .03)。管腔内乙酰胆碱在对照组中引起浓度依赖性动脉扩张，而在 VA ECMO 组中导致血管收缩 (p = .008)。各组间对 3-吗啉基-苯乙烯亚胺氯化物的扩张反应和对血清素的收缩反应没有显着差异。结论：暴露于 VA ECMO 的脑动脉肌源性反应受损，内皮功能改变。内皮细胞的改变似乎是通过一氧化氮途径介导的，在添加一氧化氮供体后注意到恢复。可以推测，这些变化可能反映了先前在该羔羊模型中报道的大脑自动调节受损的机制。
Background: Previous studies in our laboratory on newborn lambs have shown cerebral autoregulation impairment after exposure to venoarterial extracorporeal membrane oxygenation (VA ECMO), with additional studies showing an altered cerebrovascular response to NG-nitro-L-arginine methyl ester in lamb cerebral vessels in this same model.Objective: To further study the mechanisms involved in altered cerebrovascular responses in vessels exposed to VA ECMO.Design: Prospective study.Setting: Research Animal Facility at Children's National Medical Center, Washington, DC.Subject: Newborn lambs, 1-7 days of age, 4.76 +/- 0.8 kg (n = 10).Methods: Animals randomly assigned two groups, control and VA ECMO, were anesthetized, ventilated, heparinized, and kept in a normal physiologic condition. Control animals were continued on ventilatory support, whereas animals in the VA ECMO groups were placed on VA ECMO, with bypass flows maintained between 120 and 200 mL.kg(-1).min(-1) for 2.5 hrs. Isolated third-order branches of the middle cerebral arteries were studied for myotonic reactivity to increasing intraluminal pressure changes, response to acetylcholine, an endothelium-dependent vasodilator, 3-morpholinyl-sydnoneimine chloride, an endothelium-independent vasodilator, and serotonin, a direct vascular vasoconstrictor. Arterial caliber was monitored using video microscopy.Results: Myogenic constriction response was significantly decreased in the VA ECMO group compared with the control group (p = .03). Intraluminal acetylcholine caused concentration-dependent arterial dilation in the control group, whereas it resulted in vasoconstriction in the VA ECMO group (p = .008). There were no significant differences in dilation responses to 3-morpholinyl-sydnoneimine chloride and contractile responses to serotonin among the groups.Conclusion: Cerebral arteries exposed to VA ECMO had impaired myogenic responses combined with altered endothelial function. The endothelial alteration seems to be mediated through the nitric oxide pathway, with recovery noted after addition of a nitric oxide donor. It can be postulated that these changes may reflect the mechanisms for the impairment of cerebral autoregulation previously reported in this lamb model.