Castedo Evaristo, Castejón Raquel, Monguio Emilio, Ramis Sebastian, Montero Carlos G, Serrano-Fiz Santiago, Burgos Raul, Escudero Cristina, Ugarte Juan
Department of Cardiothoracic Surgery, Clinica Puerta de Hierro, Madrid, Spain.
J Cardiothorac Surg. 2007 Jan 23;2:7. doi: 10.1186/1749-8090-2-7.
There is increasing evidence that programmed cell death can be triggered during cardiopulmonary bypass (CPB) and may be involved in postoperative complications. The purpose of this study was to investigate whether apoptosis occurs during aortic valve surgery and whether modifying temperature during CPB has any influence on cardiomyocyte apoptotic death rate.
20 patients undergoing elective aortic valve replacement for aortic stenosis were randomly assigned to either moderate hypothermic (ModHT group, n = 10, 28 degrees C) or mild hypothermic (MiHT group, n = 10, 34 degrees C) CPB. Myocardial samples were obtained from the right atrium before and after weaning from CPB. Specimens were examined for apoptosis by flow cytometry analysis of annexin V-propidium iodide (PI) and Fas death receptor staining.
In the ModHT group, non apoptotic non necrotic cells (annexin negative, PI negative) decreased after CPB, while early apoptotic (annexin positive, PI negative) and late apoptotic or necrotic (PI positive) cells increased. In contrast, no change in the different cell populations was observed over time in the MiHT group. Fas expression rose after reperfusion in the ModHT group but not in MiHT patients, in which there was even a trend for a lower Fas staining after CPB (p = 0.08). In ModHT patients, a prolonged ischemic time tended to induce a higher increase of Fas (p = 0.061).
Our data suggest that apoptosis signal cascade is activated at early stages during aortic valve replacement under ModHT CPB. This apoptosis induction can effectively be attenuated by a more normothermic procedure.
越来越多的证据表明,体外循环(CPB)期间可触发程序性细胞死亡,且可能与术后并发症有关。本研究的目的是调查在主动脉瓣手术期间是否发生凋亡,以及在CPB期间改变温度是否对心肌细胞凋亡死亡率有任何影响。
20例因主动脉瓣狭窄接受择期主动脉瓣置换术的患者被随机分配至中度低温(ModHT组,n = 10,28摄氏度)或轻度低温(MiHT组,n = 10,34摄氏度)CPB组。在CPB脱机前后从右心房获取心肌样本。通过膜联蛋白V-碘化丙啶(PI)流式细胞术分析和Fas死亡受体染色检查样本的凋亡情况。
在ModHT组中,CPB后非凋亡非坏死细胞(膜联蛋白阴性,PI阴性)减少,而早期凋亡(膜联蛋白阳性,PI阴性)和晚期凋亡或坏死(PI阳性)细胞增加。相比之下,MiHT组中不同细胞群随时间未观察到变化。ModHT组再灌注后Fas表达升高,而MiHT组患者则未升高,其中CPB后甚至有Fas染色降低的趋势(p = 0.08)。在ModHT组患者中,较长的缺血时间倾向于诱导Fas更高的升高(p = 0.061)。
我们的数据表明,在中度低温CPB下进行主动脉瓣置换术的早期阶段,凋亡信号级联被激活。这种凋亡诱导可通过更接近正常体温的程序有效减弱。