Elevated circulating CD14++CD16+ intermediate monocytes are independently associated with extracardiac complications after cardiac surgery

Jana C Mossanen,Christian Stoppe,Rüdiger Autschbach,Tobias U Jansen,Tim-Philipp Simon,Frank Tacke,Lukas Buendgens,Anke Liepelt,Andreas Goetzenich,Jessica Pracht,Gernot Marx

doi:10.1038/s41598-020-57700-9

Jana C Mossanen, Christian Stoppe + Show 9 more

Open Access

https://doi.org/10.1038/s41598-020-57700-9

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Abstract

Elective cardiac surgery has low procedural complications. However, about 40% of patients develop extracardiac complications including delirium and acute kidney injury. We hypothesized that inflammatory processes and immune cell activation might be associated with these complications. We therefore prospectively included 104 patients undergoing cardiac surgery in our study. We assessed peripheral blood leukocyte populations by flow cytometry and circulating cytokines before operation, after surgery and at days one and four post-operatively. Patients undergoing cardiac surgery showed significantly elevated leukocytes and neutrophils after surgery. On the contrary, monocytes decreased after surgery and significantly increased at days 1 and 4, particularly classical (Mon1,CD14++CD16−) and intermediate (Mon2,CD14++CD16+) monocytes. While peripheral leukocyte subsets were unaltered in patients with infectious (n = 15) or cardiac complications (n = 31), post-operative leukocytes (p = 0.0016), neutrophils (p = 0.0061) and Mon2 (p = 0.0007) were clearly raised in patients developing extracardiac complications (n = 35). Using multiple logistic regression analyses, patient’s age, ICU days, number of blood transfusions and elevated post-surgery Mon2 independently predicted extracardiac complications. Our findings demonstrate that elevated Mon2 after cardiac surgery are associated with an increased risk for extracardiac complications. These findings might improve the risk estimation after cardiac operations and the role of Mon2 for inflammation in cardiac surgery.

Highlights

Despite advances in surgical and anesthetic techniques as well as enhanced postoperative care, cardiac surgery is still associated with a high risk of postoperative complications[1]
Monocytes are a key player in cardiovascular disease and atherosclerosis, and elevated CD14−CD16+ non-classical monocytes have been correlated with endothelial dysfunction and vascular oxidative stress[12,13]
We thereby demonstrate that elevated post-operative CD14++CD16+ intermediate monocytes are associated with an increased risk for extracardiac complications, which may indicate a novel role of Mon[2] in the context of inflammation related to cardiac surgery

Summary

Introduction

Despite advances in surgical and anesthetic techniques as well as enhanced postoperative care, cardiac surgery is still associated with a high risk of postoperative complications[1]. Besides typical cardiac (e.g., arrhythmia, myocardial infarction) and infectious complications (e.g., wound infection, pneumonia and sepsis), extracardiac non-infectious complications like acute kidney injury (AKI, 30%) and delirium (up to 26–52%) are frequent in patients after cardiac surgery[2,3]. In order to identify associations between monocyte subpopulations and complications after cardiac surgery, we conducted a prospective observational trial in 104 consecutive cardiac surgery patients, in which we obtained detailed circulating immune cell characteristics by multi-color flow cytometry before and sequentially after surgery. We thereby demonstrate that elevated post-operative CD14++CD16+ intermediate monocytes are associated with an increased risk for extracardiac complications, which may indicate a novel role of Mon[2] in the context of inflammation related to cardiac surgery

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