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一种用于评估补片功能和结局的新生动物大膈疝修复的不断发展的动物模型。

A growing animal model for neonatal repair of large diaphragmatic defects to evaluate patch function and outcome.

作者信息

Eastwood Mary Patrice, Joyeux Luc, Pranpanus Savitree, Van der Merwe Johannes, Verbeken Eric, De Vleeschauwer Stephanie, Gayan-Ramirez Ghislaine, Deprest Jan

机构信息

Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, Belgium.

Department of Obstetrics and Gynaecology, Prince of Songkla University, Hat Yai, Thailand.

出版信息

PLoS One. 2017 Mar 30;12(3):e0174332. doi: 10.1371/journal.pone.0174332. eCollection 2017.

Abstract

OBJECTIVES

We aimed to develop a more representative model for neonatal congenital diaphragmatic hernia repair in a large animal model, by creating a large defect in a fast-growing pup, using functional pulmonary and diaphragmatic read outs.

BACKGROUND

Grafts are increasingly used to repair congenital diaphragmatic hernia with the risk of local complications. Growing animal models have been used to test novel materials.

METHODS

6-week-old rabbits underwent fiberoptic intubation, left subcostal laparotomy and hemi-diaphragmatic excision (either nearly complete (n = 13) or 3*3cm (n = 9)) and primary closure (Gore-Tex patch). Survival was further increased by moving to laryngeal mask airway ventilation (n = 15). Sham operated animals were used as controls (n = 6). Survivors (90 days) underwent chest X-Ray (scoliosis), measurements of maximum transdiaphragmatic pressure and breathing pattern (tidal volume, Pdi). Rates of herniation, lung histology and right hemi-diaphragmatic fiber cross-sectional area was measured.

RESULTS

Rabbits surviving 90 days doubled their weight. Only one (8%) with a complete defect survived to 90 days. In the 3*3cm defect group all survived to 48 hours, however seven (78%) died later (16-49 days) from respiratory failure secondary to tracheal stricture formation. Use of a laryngeal mask airway doubled 90-day survival, one pup displaying herniation (17%). Cobb angel measurements, breathing pattern, and lung histology were comparable to sham. Under exertion, sham animals increased their maximum transdiaphragmatic pressure 134% compared to a 71% increase in patched animals (p<0.05). Patched animals had a compensatory increase in their right hemi-diaphragmatic fiber cross-sectional area (p<0.0001).

CONCLUSIONS

A primarily patched 3*3cm defect in growing rabbits, under laryngeal mask airway ventilation, enables adequate survival with normal lung function and reduced maximum transdiaphragmatic pressure compared to controls.

摘要

目的

我们旨在通过在快速生长的幼崽中制造一个大的缺损,并使用功能性肺和膈肌指标,开发一种更具代表性的大型动物模型用于新生儿先天性膈疝修复。

背景

移植物越来越多地用于修复先天性膈疝,但存在局部并发症的风险。生长动物模型已被用于测试新型材料。

方法

6周龄的兔子接受纤维光学插管、左肋下剖腹术和半膈肌切除术(近乎完全切除(n = 13)或3×3cm(n = 9)),并进行一期缝合(使用戈尔泰克斯补片)。通过改用喉罩气道通气(n = 15)进一步提高了存活率。假手术动物用作对照(n = 6)。存活90天的动物接受胸部X线检查(脊柱侧弯)、测量最大跨膈压和呼吸模式(潮气量、Pdi)。测量疝形成率、肺组织学和右半膈肌纤维横截面积。

结果

存活90天的兔子体重增加了一倍。只有一只(8%)有完全缺损的兔子存活至90天。在3×3cm缺损组中,所有兔子均存活至48小时,但有7只(78%)后来(16 - 49天)因气管狭窄形成继发呼吸衰竭死亡。使用喉罩气道使90天存活率翻倍,一只幼崽出现疝形成(17%)。Cobb角测量、呼吸模式和肺组织学与假手术组相当。在运动时,假手术动物的最大跨膈压增加了134%,而修补动物增加了71%(p<0.05)。修补动物的右半膈肌纤维横截面积有代偿性增加(p<0.0001)。

结论

在生长中的兔子中,通过喉罩气道通气,对3×3cm缺损进行一期修补,与对照组相比,能实现足够的存活率,肺功能正常,最大跨膈压降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e044/5373533/7ec13c557d03/pone.0174332.g001.jpg

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