Janssen Henrike, Felgner Larissa, Kummer Laura, Gillmann Hans-Jörg, Schrimpf Claudia, Rustum Saad, Lichtinghagen Ralf, Sahlmann Bianca, Weigand Markus A, Teebken Omke E, Theilmeier Gregor, Larmann Jan
Department of Anesthesiology, University Hospital Heidelberg, Heidelberg, Germany.
Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hanover, Germany.
Front Cardiovasc Med. 2020 Feb 18;7:13. doi: 10.3389/fcvm.2020.00013. eCollection 2020.
Patients at elevated cardiovascular risk are prone to perioperative cardiovascular complications, like myocardial injury after non-cardiac surgery (MINS). We have demonstrated in a mouse model of atherosclerosis that perioperative stress leads to an increase in plaque volume and higher plaque vulnerability. Regulatory T cells (Tregs) play a pivotal role in development and destabilization of atherosclerotic plaques. For this exploratory analysis we identified 40 patients recruited into a prospective perioperative biomarker study, who within the inclusion period underwent sequential open vascular surgery. On the basis of protein markers measured in the biomarker study, we evaluated the perioperative inflammatory response in patients' plasma before and after index surgery as well as before and after a second surgical procedure. We also analyzed available immunohistochemistry samples to describe plaque vulnerability in patients who underwent bilateral carotid endarterectomy (CEA) in two subsequent surgical procedures. Finally, we assessed if MINS was associated with sequential surgery. The inflammatory response of both surgeries was characterized by postoperative increases of interleukin-6,-10, Pentraxin 3 and C-reactive protein with no clear-cut difference between the two time points of surgery. Plaques from CEA extracted during the second surgery contained less Tregs, as measured by Foxp3 staining, than plaques from the first intervention. The 2nd surgical procedure was associated with MINS. In conclusion, we provide descriptive evidence that sequential surgical procedures involve repeat inflammation, and we hypothesize that elevated rates of cardiovascular complications after the second procedure could be related to reduced levels of intraplaque Tregs, a finding that deserves confirmatory testing and mechanistic exploration in future populations.
心血管风险升高的患者易发生围手术期心血管并发症,如非心脏手术后的心肌损伤(MINS)。我们在动脉粥样硬化小鼠模型中证明,围手术期应激会导致斑块体积增加和更高的斑块易损性。调节性T细胞(Tregs)在动脉粥样硬化斑块的形成和不稳定中起关键作用。在这项探索性分析中,我们确定了40名纳入前瞻性围手术期生物标志物研究的患者,他们在纳入期内接受了连续的开放性血管手术。基于生物标志物研究中测量的蛋白质标志物,我们评估了患者在初次手术前后以及第二次手术前后血浆中的围手术期炎症反应。我们还分析了可用的免疫组织化学样本,以描述在两次后续手术中接受双侧颈动脉内膜切除术(CEA)的患者的斑块易损性。最后,我们评估了MINS是否与连续手术有关。两次手术的炎症反应均以术后白细胞介素-6、-10、五聚体3和C反应蛋白升高为特征,两个手术时间点之间没有明显差异。通过Foxp3染色测量,第二次手术中提取的CEA斑块中的Tregs比第一次手术中的斑块少。第二次手术与MINS有关。总之,我们提供了描述性证据,表明连续手术涉及反复炎症,并且我们假设第二次手术后心血管并发症发生率升高可能与斑块内Tregs水平降低有关,这一发现值得在未来人群中进行验证性测试和机制探索。