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心肺转流新型小鼠模型。

Novel mouse model of cardiopulmonary bypass.

机构信息

Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.

Department of Nephrology, Hannover Medical School, Hannover, Germany.

出版信息

Eur J Cardiothorac Surg. 2018 Jan 1;53(1):186-193. doi: 10.1093/ejcts/ezx237.

Abstract

OBJECTIVES

Cardiopulmonary bypass (CPB) is an essential component of many cardiac interventions, and therefore, there is an increasing critical demand to minimize organ damage resulting from prolonged extracorporeal circulation. Our goal was to develop the first clinically relevant mouse model of CPB and to examine the course of extracorporeal circulation by closely monitoring haemodynamic and oxygenation parameters.

METHODS

Here, we report the optimization of device design, perfusion circuit and microsurgical techniques as well as validation of physiological functions during CPB in mice after circulatory arrest and reperfusion. Validation of the model required multiple blood gas analyses, and therefore, this initial report describes an acute model that is incompatible with survival due to the need of repetitive blood draws.

RESULTS

Biochemical and histopathological assessment of organ damage revealed only mild changes in the heart and lungs and signs of the beginning of acute organ failure in the liver and kidneys.

CONCLUSIONS

This new CPB mouse model will facilitate preclinical testing of therapeutic strategies in cardiovascular diseases and investigation of CPB in relation to different insults and pre-existing comorbidities. In combination with genetically modified mice, this model will be an important tool to dissect the molecular mechanisms involved in organ damage related to extracorporeal circulation.

摘要

目的

体外循环(CPB)是许多心脏介入的重要组成部分,因此,对于减轻长时间体外循环引起的器官损伤,存在着日益迫切的需求。我们的目标是开发首个具有临床相关性的 CPB 小鼠模型,并通过密切监测血流动力学和氧合参数来研究体外循环的过程。

方法

在这里,我们报告了设备设计、灌注回路和显微外科技术的优化,以及在循环停止和再灌注后 CPB 期间小鼠生理功能的验证。CPB 模型的验证需要多次血气分析,因此,本初始报告描述了一种急性模型,由于需要重复采血,因此无法存活。

结果

对器官损伤的生化和组织病理学评估显示,心脏和肺部仅有轻微变化,肝脏和肾脏出现急性器官衰竭的迹象。

结论

这种新的 CPB 小鼠模型将有助于心血管疾病治疗策略的临床前测试,并研究 CPB 与不同损伤和预先存在的合并症的关系。与基因修饰小鼠结合使用,该模型将成为剖析与体外循环相关的器官损伤所涉及的分子机制的重要工具。

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