Malmberg Markus, Vähäsilta Tommi, Saraste Antti, Kytö Ville, Kiss Jan, Kentala Erkki, Kallajoki Markku, Savunen Timo
Research Centre of Applied and Preventive Cardiovascular Medicine, Turku University, FIN-20520 Turku, Finland.
Eur J Cardiothorac Surg. 2006 Sep;30(3):480-4. doi: 10.1016/j.ejcts.2006.06.003. Epub 2006 Jul 20.
Apoptotic cardiomyocyte death is induced during open heart surgery, but its determinants are poorly understood. Prolonged aortic clamping time is associated with adverse clinical outcomes. The purpose of this study was to determine whether occurrence of cardiomyocyte apoptosis is related to the duration of aortic clamping in experimental pig model of cardiac surgery with cardiopulmonary bypass.
The pigs (mean weight 29 +/- 1 kg) were randomly divided to undergo cardioplegic arrest for 60 (n = 4) or 90 (n = 4) min followed by reperfusion period of 120 min. Control group (n = 5) was connected to cardiopulmonary bypass for 120 min without cardioplegic arrest. Cardiomyocyte apoptosis was detected (TUNEL assay and immunohistochemical staining of active caspase-3) in left ventricular tissue samples obtained before ischemia and after the ischemia-reperfusion period.
Apoptotic cardiomyocytes were found in all samples obtained after cardioplegic arrest and cardiopulmonary bypass alone with the TUNEL assay. The amount of apoptosis after the 120 min of cardiopulmonary bypass alone in the control group was 0.006 +/- 0.001%. Compared with this, cardiomyocyte apoptosis was increased after cardioplegic arrest. After 60 min of aortic cross-clamp the amount of apoptosis was 0.019 +/- 0.004% (p = 0.031). After 90 min of aortic cross-clamp the amount was 0.042 +/- 0.005% (p < 0.001) being significantly higher than after 60 min (p = 0.001). Aortic cross-clamp of 90 min also resulted in a detectable increase in caspase-3 activation when compared with controls.
The occurrence of cardiomyocyte apoptosis increases with prolonged aortic clamping time during open heart surgery.
在心脏直视手术期间会诱导心肌细胞发生凋亡性死亡,但其决定因素尚不清楚。主动脉阻断时间延长与不良临床结局相关。本研究的目的是确定在体外循环心脏手术的实验猪模型中,心肌细胞凋亡的发生是否与主动脉阻断时间有关。
将猪(平均体重29±1千克)随机分为两组,分别进行60分钟(n = 4)或90分钟(n = 4)的心脏停搏,随后再灌注120分钟。对照组(n = 5)连接体外循环120分钟,不进行心脏停搏。在缺血前和缺血-再灌注期后获取的左心室组织样本中检测心肌细胞凋亡(TUNEL法和活性半胱天冬酶-3的免疫组织化学染色)。
通过TUNEL法在所有心脏停搏和单纯体外循环后获取的样本中均发现了凋亡的心肌细胞。对照组单纯体外循环120分钟后的凋亡量为0.006±0.001%。与此相比,心脏停搏后心肌细胞凋亡增加。主动脉交叉阻断60分钟后,凋亡量为0.019±0.004%(p = 0.031)。主动脉交叉阻断90分钟后,凋亡量为0.042±0.005%(p < 0.001),显著高于60分钟后(p = 0.001)。与对照组相比,90分钟的主动脉交叉阻断还导致半胱天冬酶-3激活的可检测增加。
在心脏直视手术期间,心肌细胞凋亡的发生随着主动脉阻断时间的延长而增加。