Comprehensive characterization of the postoperative pericardial inflammatory response: Potential implications for clinical outcomes

Ali Fatehi Hassanabad; Friederike I Schoettler; William D T Kent; Corey A Adams; Daniel D Holloway; Imtiaz S Ali; Richard J Novick; Muhammad R Ahsan; Robert Scott McClure; Ganesh Shanmugam; William T Kidd; Teresa M Kieser; Paul W M Fedak; Justin F Deniset

doi:10.1016/j.xjon.2022.09.003

Comprehensive characterization of the postoperative pericardial inflammatory response: Potential implications for clinical outcomes

JTCVS Open. 2022 Sep 27:12:118-136. doi: 10.1016/j.xjon.2022.09.003. eCollection 2022 Dec.

Authors

Ali Fatehi Hassanabad¹, Friederike I Schoettler^{1

2}, William D T Kent¹, Corey A Adams¹, Daniel D Holloway¹, Imtiaz S Ali¹, Richard J Novick^{1

3}, Muhammad R Ahsan¹, Robert Scott McClure¹, Ganesh Shanmugam¹, William T Kidd¹, Teresa M Kieser¹, Paul W M Fedak¹, Justin F Deniset^{4

5}

Affiliations

¹ Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
² Department of Cardiac Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
³ Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
⁴ Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
⁵ Department of Cardiac Sciences, Libin Cardiovascular Institute, Calgary, Alberta, Canada.

Abstract

Objective: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Keywords: AVR, aortic valve replacement; CABG, coronary artery bypass graft; CD, cluster of differentiation; CPB, cardiopulmonary bypass; DC, dendritic cell; ECM, extracellular matrix; FS, full median sternotomy; IL, interleukin; IL-1Ra, interleukin-1 receptor antagonist; Inf DC, inflammatory dendritic cell; MICS, minimally invasive cardiac surgery; MMP, matrix metalloproteinase; MMPtot, total matrix metalloproteinases; Mφ, macrophage; NK, natural killer cell; PAOF, postoperative atrial fibrillation; PPS, postpericardiotomy syndrome; RAMT-AVR, right anterior minithoracotomy aortic valve replacement; SSC, side scatter; TGFβ, transforming growth factor-beta; TIMP, tissue inhibitor of metalloproteinases; TIMPtot, total tissue inhibitors of metalloproteinases; cDC, classical dendritic cell; conventional cardiac surgery; inflammation; minimally invasive cardiac surgery; pericardial space; postoperative pericardial fluid; sAVR, conventional full median sternotomy surgical aortic valve replacement.