左西孟旦对婴儿体外循环羔羊模型脑损伤模式的影响。

Impact of levosimendan on brain injury patterns in a lamb model of infant cardiopulmonary bypass.

机构信息

1] Pediatric Intensive Care Unit, The Royal Children's Hospital, Melbourne, Australia [2] Murdoch Children's Research Institute, Melbourne, Australia.

1] Murdoch Children's Research Institute, Melbourne, Australia [2] Department of Paediatrics, University of Melbourne, Melbourne, Australia.

出版信息

Pediatr Res. 2014 Jul;76(1):64-71. doi: 10.1038/pr.2014.51. Epub 2014 Apr 8.

DOI:10.1038/pr.2014.51

PMID:24713816

Abstract

BACKGROUND

The effects of levosimendan (Levo) on injury patterns in the immature brain following cardiopulmonary bypass (CPB) are unknown.

METHODS

Eighteen 3- to 4-wk-old anesthetized lambs, instrumented with vascular catheters and aortic and right carotid artery flow probes, were allocated to non-CPB, CPB, or CPB+Levo groups (each n = 6). After 120 min CPB with 90 min aortic cross-clamp, CPB animals received dopamine, and CPB+Levo animals both dopamine and Levo, for 4 h. All lambs then underwent brain magnetic resonance imaging, followed by postmortem brain perfusion fixation for immunohistochemical studies.

RESULTS

In CPB lambs, aortic (P < 0.05) and carotid artery (P < 0.01) blood flows fell by 29 and 30%, respectively, between 2 and 4 h after cross-clamp removal but were unchanged in the CPB+Levo group. No brain injury was detectable with magnetic resonance imaging in either CPB or CPB+Levo lambs. However, on immunohistochemical analysis, white matter astrocyte density of both groups was higher than in non-CPB lambs (P < 0.05), while white matter microglial density was higher (P < 0.05), but markers of cortical oxidative stress were less prevalent in CPB+Levo than CPB lambs.

CONCLUSION

While Levo prevented early postoperative falls in cardiac output and carotid artery blood flow in a lamb model of infant CPB, this was associated with heterogeneous neuroglial activation and manifestation of markers of oxidative stress.

摘要

背景

心肺转流（CPB）后，左西孟旦（Levo）对未成熟大脑损伤模式的影响尚不清楚。

方法

18 只 3 至 4 周龄麻醉羔羊，血管导管和主动脉及右颈动脉流量探头置入，分为非 CPB、CPB 或 CPB+Levo 组（每组 n=6）。CPB 持续 120min，主动脉夹闭 90min 后，CPB 组给予多巴胺，CPB+Levo 组给予多巴胺和 Levo，持续 4h。所有羔羊随后进行脑磁共振成像，然后进行脑灌注固定以进行免疫组织化学研究。

结果

CPB 组羔羊在夹闭解除后 2 至 4h 时，主动脉（P<0.05）和颈动脉（P<0.01）血流分别下降 29%和 30%，但 CPB+Levo 组无变化。磁共振成像在 CPB 或 CPB+Levo 组羔羊中均未检测到脑损伤。然而，在免疫组织化学分析中，两组的白质星形胶质细胞密度均高于非 CPB 组（P<0.05），而白质小胶质细胞密度更高（P<0.05），但 CPB+Levo 组皮质氧化应激标志物的出现较 CPB 组少。