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人工胎盘:早产羔羊模型体外支持期间肺的持续发育

The artificial placenta: Continued lung development during extracorporeal support in a preterm lamb model.

作者信息

Church Joseph T, Coughlin Megan A, Perkins Elena M, Hoffman Hayley R, Barks John D, Rabah Raja, Bentley J Kelley, Hershenson Marc B, Bartlett Robert H, Mychaliska George B

机构信息

Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, B560 MSRB II/SPC 5686, 1150 W. Medical Center Dr., Ann Arbor, MI, USA.

Extracorporeal Life Support Laboratory, Department of Surgery, Michigan Medicine, B560 MSRB II/SPC 5686, 1150 W. Medical Center Dr., Ann Arbor, MI, USA.

出版信息

J Pediatr Surg. 2018 Oct;53(10):1896-1903. doi: 10.1016/j.jpedsurg.2018.06.001. Epub 2018 Jun 8.

Abstract

PURPOSE

An artificial placenta (AP) utilizing extracorporeal life support (ECLS) could avoid the harm of mechanical ventilation (MV) while allowing the lungs to develop.

METHODS

AP lambs (n = 5) were delivered at 118 days gestational age (GA; term = 145 days) and placed on venovenous ECLS (VV-ECLS) with jugular drainage and umbilical vein reinfusion. Lungs remained fluid-filled. After 10 days, lambs were ventilated. MV control lambs were delivered at 118 ("early MV"; n = 5) or 128 days ("late MV"; n = 5), and ventilated. Compliance and oxygenation index (OI) were calculated. After sacrifice, lungs were procured and H&E-stained slides scored for lung injury. Slides were also immunostained for PDGFR-α and α-actin; alveolar development was quantified by the area fraction of alveolar septal tips staining double-positive for both markers.

RESULTS

Compliance of AP lambs was 2.79 ± 0.81 C compared to 0.83 ± 0.19 and 3.04 ± 0.99 for early and late MV, respectively. OI in AP lambs was lower than early MV lambs (6.20 ± 2.10 vs. 36.8 ± 16.8) and lung injury lower as well (1.8 ± 1.6 vs. 6.0 ± 1.2). Double-positive area fractions were higher in AP lambs (0.012 ± 0.003) than early (0.003 ± 0.0005) and late (0.004 ± 0.002) MV controls.

CONCLUSIONS

Lung development continues and lungs are protected from injury during AP support relative to mechanical ventilation.

LEVEL OF EVIDENCE

n/a (basic/translational science).

摘要

目的

利用体外生命支持(ECLS)的人工胎盘(AP)可避免机械通气(MV)的危害,同时使肺得以发育。

方法

AP组羔羊(n = 5)于妊娠118天(GA;足月为145天)分娩,通过颈静脉引流和脐静脉再灌注置于静脉-静脉ECLS(VV-ECLS)上。肺保持充满液体状态。10天后,对羔羊进行通气。MV对照组羔羊于118天(“早期MV”;n = 5)或128天(“晚期MV”;n = 5)分娩并进行通气。计算顺应性和氧合指数(OI)。处死后,获取肺组织并制作苏木精-伊红(H&E)染色切片,对肺损伤进行评分。切片还进行血小板衍生生长因子受体-α(PDGFR-α)和α-肌动蛋白免疫染色;通过对两种标志物均呈双阳性染色的肺泡间隔尖端的面积分数来量化肺泡发育情况。

结果

AP组羔羊的顺应性为2.79±0.81 C,而早期MV组和晚期MV组分别为0.83±0.19和3.04±0.99。AP组羔羊的OI低于早期MV组羔羊(6.20±2.10对36.8±16.8),肺损伤也更低(1.8±1.6对6.0±1.2)。AP组羔羊的双阳性面积分数(0.012±0.003)高于早期(0.003±0.0005)和晚期(0.004±0.002)MV对照组。

结论

相对于机械通气,在AP支持期间肺发育持续进行且肺免受损伤。

证据水平

无(基础/转化科学)。

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