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

Cardiovasc Pathol. 2024 Nov-Dec:73:107686. doi: 10.1016/j.carpath.2024.107686. Epub 2024 Aug 19.

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.

Keywords: Cardiac surgery; Inflammation; Myocardial injury; Pericardial space; Preclinical study.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal*
  • Inflammation Mediators* / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Myocardial Reperfusion Injury / immunology
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Pericardial Fluid / metabolism
  • Pericardium / immunology
  • Pericardium / metabolism
  • Pericardium / pathology
  • Sus scrofa
  • Swine
  • Time Factors

Substances

  • Inflammation Mediators
  • Cytokines