The Effect of Coronary Artery Bypass Surgery on Interleukin-18 Concentration and Biomarkers Related to Vascular Endothelial Glycocalyx Degradation

Abstract

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.

Keywords: cardiac surgery; endothelial glycocalyx; hyaluronic acid; inflammation; interleukin-18; syndecan-1.

Figure 1

Comparison of the absolute number of leukocytes (A), the concentration of CRP (B), and the concentration of cTnT (C) in the on-pump group (□) and the off-pump group (■) before surgery (T1) and 24 h (T2) and 72 h (T3) after surgery in peripheral blood. * Level of statistical significance: p < 0.05. Data are expressed as median and 25th–75th percentile. CRP—C-reactive protein, cTnT—cardiac troponin T.

Figure 2

Dynamic changes in and comparison of the concentration of interleukin-18 between the on-pump group (□) and the off-pump group (■) before surgery (T1) and 24 h (T2) and 72 h (T3) after surgery in peripheral blood (A) and in the coronary sinus and aortic root during surgery before bypass grafting was performed (B). * Level of statistical significance: p < 0.05. Data are expressed as median and 25th–75th percentile.

Figure 3

Dynamic changes in and comparison of the plasma concentration of syndecan-1 (A) and hyaluronic acid (B) between the on-pump group (□) and the off-pump group (■) at different time points: before surgery (T1) and 24 h (T2) and 72 h (T3) after surgery. * Level of statistical significance: p < 0.05. Data are expressed as median and 25th–75th percentile.

Figure 4

Comparison of the concentration of syndecan-1 (A) and hyaluronic acid (B) in the coronary sinus and aortic root between the on-pump group (□) and the off-pump group (■) during surgery before bypass grafting was performed. Data are expressed as median and 25th–75th percentile.

Figure 5

Summary of the study results with clinical implications. Cardiac surgery leads to an increased inflammatory response that triggers degradation of EG. A more intense inflammatory response leads to higher EG degradation, which in turn triggers IRI. IRI increases postoperative complications and prolongs the recovery time and positive outcome. CRP—C-reactive protein, cTnT—cardiac troponin, EG—endothelial glycocalyx, IL—interleukin, Lkc—leukocytes, IRI—ischemia–reperfusion injury. ↑, increase; ↓, decrease.

Figure 6

Flow diagram of the study protocol.