(P180) DETERMINING THE TRANSLATIONAL POTENTIAL OF HUMAN PERICARDIAL FLUID TO IMPROVE CLINICAL OUTCOMES IN CARDIAC SURGERY

Background: The pericardial space, which contains pericardial fluid (PF), maintains homeostatic conditions that facilitates optimal heart function. The loss of PF during surgery perturbs the equilibrium of this environment, contributing to postsurgical complications, including postoperative pericardial adhesion formation (PPAF) and postoperative atrial fibrillation (POAF), both of which involve immune-mediated pathways. We have yet to fully understand the exact pathophysiology of these adverse events. This study aimed to establish the immune profile of human PF, determine whether specific markers can drive inflammatory processes, such as fibrosis, and elucidate the underlying mechanisms that can result in such phenomena.

METHODS AND RESULTS: PF was collected from patients undergoing elective cardiac surgery. Multiplex analysis was performed on the PF to determine the composition of inflammatory chemokines, cytokines, growth factors, matrix metalloproteinases (MMP), and tissue inhibitors of matrix metalloproteinases (TIMP). To explore the source of these mediators, multiplex analysis was conducted on cultured media from the pericardium, right atrial appendage, and pericardial adipose tissue. Mass spectrometry revealed the proteomic content of PF. Gel contraction assay was used to investigate the fibrotic potential of PF. RNA-sequencing was used to elucidate the mechanisms driving the pro- or anti-fibrotic properties of PF.
Sixty-five panel multiplex analysis was performed on the PF of 109 patients, where 64 were male, and the average age was 68±8. Forty patients underwent isolated CABG surgery; 38 had a valvular procedure; and 31 had a concomitant intervention. Levels of interferon gamma-induced protein 10 and interleukin (IL)-23 were higher in the CABG cohort (p=0.01). Among all patients, transforming growth factor beta-1 (TGFb-1) was the highest expressed growth factor (204.92±112.26 pg/mL). Between the two patient groups, there was no significant difference in the levels of MMP-2 (p=0.07) and TIMP-1 (p=0.09) and -2 (p=0.06). IL-23 was equally produced by myocardial tissue, pericardial adipose tissue, and the pericardium. Proteomic analysis found a high level of plasma proteins present in PF, which was higher in the CABG patients (p=0.04). PF immune cells reduced the fibrotic activity of human cardiac fibroblast in vitro. Conversely, the acellular component drove fibrotic activity in human cardiac fibroblasts. This was mediated through TGFb and bone morphogenic protein signaling pathways (Fig 1).

Conclusion: For the first time, we establish a comprehensive profile for the immune mediators present in human PF. We show that PF immune cells have anti-fibrotic properties while the acellular component has pro-fibrotic characteristics and suggest putative mechanisms that can explain such observations.