Fatehi Hassanabad Ali, Schoettler Friederike I, Kent William D T, Adams Corey A, Holloway Daniel D, Ali Imtiaz S, Novick Richard J, Ahsan Muhammad R, McClure Robert Scott, Shanmugam Ganesh, Kidd William T, Kieser Teresa M, Fedak Paul W M, Deniset Justin F
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Department of Cardiac Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
JTCVS Open. 2022 Sep 27;12:118-136. doi: 10.1016/j.xjon.2022.09.003. eCollection 2022 Dec.
There is a paucity of data on the inflammatory response that takes place in the pericardial space after cardiac surgery. This study provides a comprehensive assessment of the local postoperative inflammatory response.
Forty-three patients underwent cardiotomy, where native pericardial fluid was aspirated and compared with postoperative pericardial effluent collected at 4, 24, and 48 hours' postcardiopulmonary bypass. Flow cytometry was used to define the levels and proportions of specific immune cells. Samples were also probed for concentrations of inflammatory cytokines, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs).
Preoperatively, the pericardial space mainly contains macrophages and T cells. However, the postsurgical pericardial space was populated predominately by neutrophils, which constituted almost 80% of immune cells present, and peaked at 24 hours. When surgical approaches were compared, minimally invasive surgery was associated with fewer neutrophils in the pericardial space at 4 hours' postsurgery. Analysis of the intrapericardial concentrations of inflammatory mediators showed interleukin-6, MMP-9, and TIMP-1 to be highest postsurgery. Over time, MMP-9 concentrations decreased significantly, whereas TIMP-1 levels increased, resulting in a significant reduction of the ratio of MMP:TIMP after surgery, suggesting that active inflammatory processes may influence extracellular matrix remodeling.
These results show that cardiac surgery elicits profound alterations in the immune cell profile in the pericardial space. Defining the cellular and molecular mediators that drive pericardial-specific postoperative inflammatory processes may allow for targeted therapies to reduce immune-mediated complications.
关于心脏手术后心包腔内发生的炎症反应的数据较少。本研究对术后局部炎症反应进行了全面评估。
43例患者接受了心脏切开术，抽取了心包内的液体，并与体外循环后4小时、24小时和48小时收集的术后心包积液进行比较。采用流式细胞术确定特定免疫细胞的水平和比例。还检测了样本中炎性细胞因子、基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）的浓度。
术前，心包腔内主要含有巨噬细胞和T细胞。然而，术后心包腔内主要是中性粒细胞，占免疫细胞的近80%，并在24小时达到峰值。比较手术方式时，微创手术术后4小时心包腔内中性粒细胞较少。心包内炎性介质浓度分析显示，白细胞介素-6、MMP-9和TIMP-1在术后最高。随着时间的推移，MMP-9浓度显著降低，而TIMP-1水平升高，导致术后MMP:TIMP比值显著降低，表明活跃的炎症过程可能影响细胞外基质重塑。
这些结果表明，心脏手术会引起心包腔内免疫细胞谱的深刻变化。确定驱动心包特异性术后炎症过程的细胞和分子介质可能有助于采用靶向治疗来减少免疫介导的并发症。
