Comprehensive characterization of the postoperative pericardial inflammatory response: Potential implications for clinical outcomesCentral MessagePerspective
Ali Fatehi Hassanabad, MD, MSc,
Friederike I. Schoettler, MD,
William D.T. Kent, MD, MSc,
Corey A. Adams, MD, MSc,
Daniel D. Holloway, MD, MSc,
Imtiaz S. Ali, MD,
Richard J. Novick, MD, MSc,
Muhammad R. Ahsan, MBBS,
Robert Scott McClure, MD, MSc,
Ganesh Shanmugam, MD,
William T. Kidd, MD,
Teresa M. Kieser, MD, PhD,
Paul W.M. Fedak, MD, PhD,
Justin F. Deniset, PhD
Affiliations
Ali Fatehi Hassanabad, MD, MSc
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Friederike I. Schoettler, MD
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
William D.T. Kent, MD, MSc
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Corey A. Adams, MD, MSc
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Daniel D. Holloway, MD, MSc
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Imtiaz S. Ali, MD
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Richard J. Novick, MD, MSc
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Muhammad R. Ahsan, MBBS
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Robert Scott McClure, MD, MSc
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Ganesh Shanmugam, MD
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
William T. Kidd, MD
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Teresa M. Kieser, MD, PhD
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Paul W.M. Fedak, MD, PhD
Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Justin F. Deniset, PhD
Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Cardiac Sciences, Libin Cardiovascular Institute, Calgary, Alberta, Canada; Address for reprints: Justin F. Deniset, PhD, Department of Physiology & Pharmacology, Department of Cardiac Sciences, Libin Cardiovascular Institute Cumming School of Medicine, Health Research Innovation Centre, University of Calgary, 3330 Hospital Dr NW, Room GAC56, Calgary, Alberta, Canada, T2N 4N1.
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.
