Acute pericardial postischemic inflammatory responses: Characterization using a preclinical porcine model

Cardiovascular Pathology, vol. 73, pp. 107686

Abstract

BACKGROUND: Pericardial fluid (PF) contains cells, proteins, and inflammatory mediators, such as cytokines, chemokines, growth factors, and matrix metalloproteinases. To date, we lack an adequate understanding of the inflammatory response that acute injury elicits in the pericardial space. OBJECTIVE: To characterize the inflammatory profile in the pericardial space acutely after ischemia/reperfusion. METHODS: Pigs were used to establish a percutaneous ischemia/reperfusion injury model. PF was removed from pigs at different time points postanesthesia or postischemia/reperfusion. Flow cytometry was used to characterize the immune cell composition of PF, while multiplex analysis was performed on the acellular portion of PF to determine the concentration of inflammatory mediators. There was a minimum of 3 pigs per group. RESULTS: While native PF mainly comprises macrophages, we show that neutrophils are the predominant inflammatory cell type in the pericardial space after injury. The combination of acute ischemia/reperfusion (IR) and repeatedly accessing the pericardial space significantly increases the concentration of interleukin-1 beta (IL-1β) and interleukin-1 receptor antagonist (IL-1ra). IR significantly increases the pericardial concentration of TGFβ1 but not TGFβ2. We observed that repeated manipulation of the pericardial space can also drive a robust pro-inflammatory response, resulting in a significant increase in immune cells and the accumulation of potent inflammatory mediators in the pericardial space. CONCLUSION: In the present study, we show that both IR and surgical manipulation can drive robust inflammatory processes in the pericardial space, consisting of an increase in inflammatory cytokines and alteration in the number and composition of immune cells.

Authors 15

1. Ali Fatehi Hassanabad

   University of Calgary · Libin Cardiovascular Institute of Alberta

   Affiliation as printed

   Department of Cardiac Sciences, Section of Cardiac Surgery, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

2. Jeannine Turnbull

   University of Calgary · Libin Cardiovascular Institute of Alberta

   Affiliation as printed

   Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

3. Friederike Irmgard Schoettler Aachen Medical Faculty Department of Cardiac Surgery

   RWTH Aachen University · Düsseldorf University Hospital · Heinrich Heine University Düsseldorf · University of Calgary · Libin Cardiovascular Institute of Alberta

   Affiliation as printed

   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; Department of Cardiac Surgery, Medical Faculty, RWTH Aachen University, Aachen, Germany

4. Mortaza Fatehi Hassanabad

   University of Alberta

   Affiliation as printed

   Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada

5. Emilie de Chantal

   University of Calgary · Libin Cardiovascular Institute of Alberta

   Affiliation as printed

   Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

6. Jameson A. Dundas

   University of Calgary · Libin Cardiovascular Institute of Alberta

   Affiliation as printed

   Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

7. Carmina Albertine Isidoro

   University of Calgary · Libin Cardiovascular Institute of Alberta

   Affiliation as printed

   Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

8. Sun Min Kim

   University of Calgary · Libin Cardiovascular Institute of Alberta

   Affiliation as printed

   Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

9. Rosalie Morrish

   University of Calgary · Libin Cardiovascular Institute of Alberta

   Affiliation as printed

   Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

10. Barb McLellan

    University of Calgary · Libin Cardiovascular Institute of Alberta

    Affiliation as printed

    Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

11. Anna N. Zarzycki Aachen Medical Faculty Department of Cardiac Surgery

    RWTH Aachen University · University of Calgary · Libin Cardiovascular Institute of Alberta

    Affiliation as printed

    Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Cardiac Surgery, Medical Faculty, RWTH Aachen University, Aachen, Germany

12. Darrell D. Belke

    University of Calgary · Libin Cardiovascular Institute of Alberta

    Affiliation as printed

    Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

13. Bryan Har

    University of Calgary · Libin Cardiovascular Institute of Alberta

    Affiliation as printed

    Department of Cardiac Sciences, Section of Cardiology, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

14. Paul W.M. Fedak

    University of Calgary · Libin Cardiovascular Institute of Alberta

    Affiliation as printed

    Department of Cardiac Sciences, Section of Cardiac Surgery, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

15. Justin Deniset

    University of Calgary · Libin Cardiovascular Institute of Alberta

    Affiliation as printed

    Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address: jdeniset@ucalgary.ca