Herajärvi Johanna, Anttila Tuomas, Dimova Elitsa Y, Laukka Tuomas, Myllymäki Mikko, Haapanen Henri, Olenchock Benjamin A, Tuominen Hannu, Puistola Ulla, Karihtala Peeter, Kiviluoma Kai, Koivunen Peppi, Anttila Vesa, Juvonen Tatu
a Research Unit of Surgery, Anesthesia and Intensive Care , University of Oulu and MRC Oulu , Oulu, Finland.
b Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine , Oulu Center for Cell-Matrix Research, University of Oulu , Oulu , Finland.
Scand Cardiovasc J. 2017 Aug;51(4):233-241. doi: 10.1080/14017431.2017.1319574. Epub 2017 Apr 24.
During aortic and cardiac surgery, risks for mortality and morbidity are inevitable. Surgical setups involving deep hypothermic circulatory arrest (DHCA) are effective to achieve organ protection against ischemic injury. The aim of this study was to identify humoural factors mediating additive protective effects of remote ischemic preconditioning (RIPC) in a porcine model of DHCA.
Twenty-two pigs were randomized into the RIPC group (n = 11) and the control group (n = 11). The RIPC group underwent four 5-minute hind limb ischemia-reperfusion cycles prior to cardiopulmonary bypass and DHCA. All animals underwent identical surgical procedures including 60 min DHCA at 18 °C. Blood samples were collected from vena cava and sagittal sinus at several time points. After the 8-hour follow-up period, the brain, heart, and kidney tissue samples were collected for tissue analyses.
Serum levels of brain damage marker S100B recovered faster in the RIPC group, after 4 hours of the arrest, (p < .05). Systemic lactate levels were lower and cardiac index was higher in the RIPC group postoperatively. Immunohistochemical cerebellum regional scores of antioxidant response regulator Nrf2 were better in the RIPC group (mean: 1.1, IQR: 0.0-2.5) compared with the control group (mean: 0.0, IQR: 0.0-0.0), reaching borderline statistical significance (p = .064). RIPC induced detectable modulations of plasma proteome and metabolites.
The faster recovery of S100B, lower systemic lactate levels and favourable regional antioxidant response suggest possible neuronal cellular and mitochondrial protection by RIPC, whereas better cardiac index underlines functional effects of RIPC. The exact humoural factor remains unclear.
在主动脉和心脏手术期间,死亡和发病风险不可避免。涉及深低温循环停搏(DHCA)的手术设置对于实现器官免受缺血性损伤的保护是有效的。本研究的目的是在猪DHCA模型中确定介导远程缺血预处理(RIPC)附加保护作用的体液因素。
22头猪被随机分为RIPC组(n = 11)和对照组(n = 11)。RIPC组在体外循环和DHCA之前进行四个5分钟的后肢缺血-再灌注周期。所有动物均接受相同的外科手术,包括在18°C下进行60分钟的DHCA。在几个时间点从腔静脉和矢状窦采集血样。在8小时的随访期后,采集脑、心脏和肾脏组织样本进行组织分析。
在停搏4小时后,RIPC组脑损伤标志物S100B的血清水平恢复得更快(p < 0.05)。RIPC组术后全身乳酸水平较低,心脏指数较高。与对照组(平均值:0.0,四分位间距:0.0 - 0.0)相比,RIPC组抗氧化反应调节因子Nrf2的免疫组化小脑区域评分更好(平均值:1.1,四分位间距:0.0 - 2.5),达到边缘统计学意义(p = 0.064)。RIPC诱导了血浆蛋白质组和代谢物的可检测调节。
S100B的更快恢复、较低的全身乳酸水平和良好的区域抗氧化反应表明RIPC可能对神经元细胞和线粒体有保护作用,而更好的心脏指数强调了RIPC的功能作用。确切的体液因素仍不清楚。