A cardiopulmonary bypass with deep hypothermic circulatory arrest rat model for the investigation of the systemic inflammation response and induced organ damage.
A cardiopulmonary bypass with deep hypothermic circulatory arrest rat model for the investigation of the systemic inflammation response and induced organ damage.
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DOI：
10.1186/s12950-014-0026-3
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Boeken U
中科院分区：
文献类型：
--
作者：
Engels M;Bilgic E;Pinto A;Vasquez E;Wollschläger L;Steinbrenner H;Kellermann K;Akhyari P;Lichtenberg A;Boeken U
心脏搭桥术（CPB）是心脏手术中常用的技术。然而，CPB与全身炎症反应综合征（SIRS）的强烈诱导相关，SIRS与缺血和再灌注结合可导致多器官衰竭。本研究的目的是建立和表征一种CPB大鼠模型，该模型结合深低温停循环，特别关注炎症反应和器官损伤的程度，作为对抗SIRS和I/R诱导的器官损伤的新疗法的基础。将雄性Wistar大鼠（n = 6）插管用于CPB，连接至心肺机（HLM）并冷却至16°C的温度，然后在全身缺血的情况下进行45分钟的深低温停循环。停搏后复温，再灌注60分钟。在整个CPB过程中记录血液动力学和生命参数。仅在整个再灌注期间显示窦性心律的动物用于分析。对大鼠实施安乐死并收获组织样品。进行血气分析并采集血样。通过分析激酶和应激蛋白的蛋白水平和磷酸化状态来检查器官损伤的诱导。将结果与未接受CPB的动物（n = 6）进行比较。CPB诱导白细胞增多，白细胞介素-6和TNF-α血浆值升高，表明存在炎症反应。组织损伤和功能障碍的标志物，如肌钙蛋白T、肌酐和AST升高。在所有检查的器官中诱导STAT 3磷酸化。MAPK的激活和热休克蛋白的诱导以器官特异性的方式发生，在心脏、肺和肾脏中具有最显著的影响。呈现的CPB大鼠模型显示SIRS的诱导和特异性信号级联的激活。在DHCA期间似乎不引起SIRS，并且主要在再灌注期间引起。该模型可能适用于测试在有和没有DHCA的心脏大手术中应用的治疗剂的疗效。
Cardiopulmonary bypass (CPB) is a commonly used technique in cardiac surgery. CPB is however associated with a strong induction of systemic inflammatory response syndrome (SIRS) which in conjunction with ischemia and reperfusion may lead to multiple organ failure. The aim of the study was to establish and characterize a CPB rat model incorporating deep hypothermic circulatory arrest with a specific focus on the extent of the inflammatory reactions and organ damage as a groundwork for novel therapeutics against SIRS and I/R induced organ injury. Male Wistar rats (n = 6) were cannulated for CPB, connected to a heart-lung-machine (HLM) and cooled to a temperature of 16°C before they underwent 45 minutes of deep hypothermic circulatory arrest with global ischaemia. Arrest was followed by rewarming and 60 minutes of reperfusion. Haemodynamic and vital parameters were recorded throughout the CPB procedure. Only animals displaying sinus rhythm throughout reperfusion were utilized for analysis. Rats were euthanized and tissue samples were harvested. Blood gas analysis was performed and blood samples were taken. Induction of organ damage was examined by analysis of protein levels and phosphorylation status of kinases and stress proteins. Results were compared to animals (n = 6) which did not undergo CPB. CPB induced leucocytosis and an increase of interleukin-6 and TNF-α plasma values indicating an inflammatory response. Markers of tissue damage and dysfunction, such as troponin T, creatinine and AST were elevated. Phosphorylation of STAT3 was induced in all examined organs. Activation of MAPK and induction of heat shock proteins occurred in an organ-specific manner with most pronounced effects in heart, lungs and kidneys. The presented CPB rat model shows the induction of SIRS and activation of specific signalling cascades. SIRS seems not to be provoked during DHCA and is elicited mainly during reperfusion. This model might be suitable to test the efficacy of therapeutics applied in major heart surgery with and without DHCA.
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DOI：
10.1007/s00534-009-0155-x
发表时间：
2009-11-01
期刊：
JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY
影响因子：
--
作者：
King, LaShonda A.;Toledo, Alexander H.;Toledo-Pereyra, Luis H.
通讯作者：
Toledo-Pereyra, Luis H.
DOI：
10.1016/j.jtcvs.2012.11.072
发表时间：
2013-03-01
影响因子：
6
作者：
Griepp, Randall B.;Di Luozzo, Gabriele
通讯作者：
Di Luozzo, Gabriele
影响因子：
8.8
作者：
Cuschieri, J;Maier, RV
通讯作者：
Maier, RV
DOI：
10.1016/j.jtcvs.2009.11.022
发表时间：
2010-10-01
影响因子：
6
作者：
Maganti, Manjula;Badiwala, Mitesh;Rao, Vivek
通讯作者：
Rao, Vivek
影响因子：
9.8
作者：
Aouifi, A;Piriou, V;Lehot, JJ
通讯作者：
Lehot, JJ