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在婴儿体外循环心脏直视手术后,血液、delNido 或 Custodiol 心脏停搏液对心肌热休克蛋白表达和细胞凋亡反应的急性变化。

Acute Changes in Myocardial Expression of Heat Shock Proteins and Apoptotic Response Following Blood, delNido, or Custodiol Cardioplegia in Infants Undergoing Open-Heart Surgery.

机构信息

Pediatric Cardiovascular Surgery Clinic, Kartal Koşuyolu High Specialization Training and Research Hospital, Health Sciences University, Denizer Road No:2, 34846, Cevizli-Kartal/Istanbul, Turkey.

Department of Molecular Biology and Genetics, Institute of Graduate Studies in Sciences, Istanbul University, Istanbul, Turkey.

出版信息

Pediatr Cardiol. 2022 Mar;43(3):567-579. doi: 10.1007/s00246-021-02759-y. Epub 2021 Oct 25.

Abstract

Stress caused by cardioplegic ischemic arrest was shown to alter the expression levels of heat shock proteins (Hsp), but little is known about their effects, particularly on pediatric hearts. This study aimed to investigate whether myocardial cellular stress and apoptotic response changes due to different cardioplegia (CP) solutions during cardiopulmonary bypass (CPB) in infants and to determine their influence on surgical/clinical outcomes. Therefore, twenty-seven infants for surgical closure of ventricular septal defect were randomly assigned to a CP solution: normothermic blood (BCP), delNido (dNCP), and Custodiol (CCP). Hsp levels and apoptosis were determined by immunoblotting in cardiac tissue from the right atrium before and after CP, and their correlations with cardiac parameters were evaluated. No significant change was observed in Hsp27 levels. Hsp60, Hsp70, and Hsp90 levels decreased significantly in the BCP-group but increased markedly in the CCP-group. Decreased Hsp60 and increased Hsp70 expression were detected in dNCP-group. Importantly, apoptosis was not observed in dNCP- and CCP-groups, whereas marked increases in cleaved caspase-3 and -8 were determined after BCP. Serum cardiac troponin-I (cTn-I), myocardial injury marker, was markedly lower in the BCP- and dNCP-groups than CCP. Additionally, Hsp60, Hsp70, and Hsp90 levels were positively correlated with aortic cross-clamp time, total perfusion time, and cTn-I release. Our findings show that dNCP provides the most effective myocardial preservation in pediatric open-heart surgery and indicate that an increase in Hsp70 expression may be associated with a cardioprotective effect, while an increase in Hsp60 and Hsp90 levels may be an indicator of myocardial damage during CPB.

摘要

心脏停搏引起的应激被证明会改变热休克蛋白(Hsp)的表达水平,但人们对其影响知之甚少,特别是对儿科心脏。本研究旨在探讨不同心脏停搏液(CP)在婴儿体外循环(CPB)期间对心肌细胞应激和凋亡反应的影响,并确定其对手术/临床结果的影响。因此,将 27 名接受室间隔缺损手术修补的婴儿随机分配到 CP 液组:常温血(BCP)、delNido(dNCP)和 Custodiol(CCP)。在 CP 前后通过免疫印迹法测定右心房心肌组织中的 Hsp 水平和凋亡,并评估其与心脏参数的相关性。Hsp27 水平无显著变化。BCP 组 Hsp60、Hsp70 和 Hsp90 水平显著降低,CCP 组明显升高。dNCP 组检测到 Hsp60 降低和 Hsp70 表达增加。重要的是,dNCP 和 CCP 组未观察到凋亡,而 BCP 后检测到 cleaved caspase-3 和 -8 明显增加。BCP 和 dNCP 组的血清心肌肌钙蛋白 I(cTn-I),心肌损伤标志物,明显低于 CCP。此外,Hsp60、Hsp70 和 Hsp90 水平与主动脉阻断时间、总灌注时间和 cTn-I 释放呈正相关。我们的研究结果表明,dNCP 为小儿心脏直视手术提供了最有效的心肌保护作用,并表明 Hsp70 表达增加可能与心脏保护作用相关,而 Hsp60 和 Hsp90 水平升高可能是 CPB 期间心肌损伤的标志物。

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