The pericardial space: Biological and translational insights into a non-inert milieu

The pericardial space is a biologically active inflammatory and cellular microenvironment with growing relevance to cardiac disease and surgical practice. Pericardial fluid contains bioactive mediators that frequently exceed systemic concentrations, and the anatomical proximity of this compartment to the myocardium highlights its potential role in cardiac pathology and post-surgical complications. Despite increasing recognition of its importance, the immune biology of the pericardial space remains incompletely characterized, and significant gaps persist in our understanding of its molecular and cellular dynamics. Available evidence indicates that pericardial cytokines, chemokines, and immune cell populations exhibit disease- and injury-specific patterns with relevance in myocardial ischemia, heart failure, cardiac transplantation, and post-operative atrial fibrillation. Following cardiac surgery, pericardial fluid sampled at pericardial opening and from post-operative mediastinal drainage demonstrates a compartmentalized inflammatory response with elevated pro-inflammatory mediators that exceed corresponding systemic levels. In the setting of ischemic injury, pericardial fluid is enriched in markers of tissue remodelling and fibrosis. After myocardial infarction, neutrophils become the dominant inflammatory cell, while resident pericardial macrophages are depleted but subsequently recover during the reparative phase. Collectively, these findings support a framework in which the pericardial space functions as a dynamic signalling reservoir that both reflects and modulates cardiac inflammatory and reparative processes. This review summarizes the current evidence on pericardial immune cells, cytokines, chemokines, and emerging molecular mediators across cardiac surgical populations and the spectrum of ischemic injury, heart failure, and post-operative atrial fibrillation.