Surgical myocardial revascularization, regardless of the technique used, causes ischemia–reperfusion injury (IRI) in the myocardium mediated by inflammation and degradation of the endothelial glycocalyx (EG). We investigated the difference between on-pump and off-pump techniques in terms of the concentration of proinflammatory interleukin (IL)-18 and the EG degradation products syndecan-1 and hyaluronic acid measured by ELISA in the peripheral and cardiac circulation during open heart surgery and in the early postoperative period. The concentration of IL-18, C-reactive protein (CRP), and cardiac troponin T (cTnT) and the leukocyte count increased statistically significantly in revascularized patients at 24 and 72 h after revascularization compared to the beginning of the procedure and was always statistically significantly higher in on-pump patients. Syndecan-1 and hyaluronic acid only increased in on-pump patients 24 and 72 h after revascularization. IL-18 correlated positively with syndecan-1 and CRP only in the pump setting and with the number of leukocytes in both revascularization regimens 24 and 72 h after the surgery. cTnT and hyaluronic acid did not correlate with IL-18. Our results suggest that IL-18 plays an important role in the early inflammatory response in patients during open heart surgery and in the early postoperative period, leading to additional damage to the EG, while it is probably not responsible for myocardial necrosis. It could serve as a biomarker to identify high-risk patients and as a therapeutic target to reduce inflammation and EG degradation. In addition, measurement of IL-18 could help improve the treatment, recovery, and outcomes of patients after heart surgery.

Open-heart surgery with cardiopulmonary bypass (CPB) is a high-risk procedure with significant morbidity and mortality. CPB, tissue injury, blood loss, endotoxemia and ischemia–reperfusion injury induce a pronounced systemic inflammatory response, leading to endothelial glycocalyx (EG) damage and vascular endothelial dysfunction. Consequently, immune cells, reactive oxygen species, and enzymes gain free access to vascular endothelial cells, resulting in their dysfunction and enhancing inflammation, vascular permeability, and microvascular impairment. EG degradation is most commonly assessed by measuring the circulating levels of its degradation products. Additionally, CPB triggers an early inflammatory response that is characterized by the secretion of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha, and IL-18, which play roles in initiating the process of EG injury. EG damage is further propagated by the sustained release of cytokines, inhibiting the regeneration of the glycocalyx layer. Heparanase and matrix metalloproteinases are enzymatic pathways involved in cytokine-mediated EG degradation after cardiac surgery, and the balance between the pro- and anti-inflammatory cytokines determines the magnitude and duration of the inflammatory response and EG impairment, which correlates with adverse clinical outcomes, including myocardial dysfunction, acute lung and kidney injury, neurological complications, and prolonged need for intensive care. Thus, identifying patients with an exaggerated cytokine response could potentially provide more personalized therapy based on the circulating biomarkers of EG shedding, and cytokine-directed preservation of EG represents a promising therapeutic strategy in vascular dysfunction prevention during and after open-heart surgery. In this review, we summarize the current knowledge on cytokine-mediated EG impairment following open-heart surgery with CPB.