Since its introduction, the number of heart surgeries has risen continuously. It is a high-risk procedure, usually involving cardiopulmonary bypass, which is associated with an inflammatory reaction that can lead to perioperative and postoperative organ dysfunction. The extent of complications following cardiac surgery has been the focus of interest for several years because of their impact on patient outcomes. Recently, numerous scientific efforts have been made to uncover the complex mechanisms of interaction between inflammation, oxidative stress, and endothelial dysfunction that occur after cardiac surgery. Numerous factors, such as surgical and anesthetic techniques, hypervolemia and hypovolemia, hypothermia, and various drugs used during cardiac surgery trigger the development of systemic inflammatory response and the release of oxidative species. They affect the endothelium, especially endothelial glycocalyx (EG), a thin surface endothelial layer responsible for vascular hemostasis, its permeability and the interaction between leukocytes and endothelium. This review highlights the current knowledge of the molecular mechanisms involved in endothelial dysfunction, particularly in the degradation of EG. In addition, the major inflammatory events and oxidative stress responses that occur in cardiac surgery, their interaction with EG, and the clinical implications of these events have been summarized and discussed in detail. A better understanding of the complex molecular mechanisms underlying cardiac surgery, leading to endothelial dysfunction, is needed to improve patient management during and after surgery and to develop effective strategies to prevent adverse outcomes that complicate recovery.

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.

Background/Objectives: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response that may contribute to postoperative organ dysfunction. However, the effects of pulsatile and non-pulsatile CPB on the inflammatory response remain incompletely understood. This study investigated the perioperative dynamics of interleukin (IL)-1β, IL-18, and IL-18 binding protein (IL-18BP), as pre-specified secondary inflammatory biomarker analysis of a prospective, multicentric, randomized trial (ISRCTN11243508), in patients undergoing cardiac surgery with pulsatile or non-pulsatile CPB and evaluated their relationships with routine inflammatory and myocardial injury biomarkers. Methods: In this study 142 patients undergoing elective cardiac surgery were randomized to pulsatile (Group P) or non-pulsatile (Group NP) CPB, and 129 were analyzed (pulsatile, n = 63; non-pulsatile, n = 66). Blood samples were collected before surgery and at five postoperative time points. Plasma concentrations of IL-1β, IL-18, and IL-18BP were measured by ELISA. Leukocyte count, C-reactive protein (CRP), procalcitonin (PCT), high-sensitivity cardiac troponin I (hsTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also analyzed. The trial was powered for its primary outcome; for these secondary outcomes the achieved sample size had 80% power to detect between-group ratios of geometric means of approximately 1.27 (IL-18), 1.41 (IL-18BP) and 1.38 (IL-1β). Results: Cardiac surgery with CPB induced a marked postoperative inflammatory response in both groups: leukocyte count, CRP, PCT, IL-18, IL-18BP, hsTnI and NT-proBNP increased significantly after surgery, whereas IL-1β remained essentially unchanged. In the pre-specified confirmatory comparison of postoperative peak concentrations, no biomarker differed significantly between groups. The 95% confidence intervals of this comparison exclude a pulsatile-flow effect on peak IL-18 larger than a 15% reduction or 19% increase, and on peak IL-18BP larger than a 26% reduction or 20% increase. A supporting mixed model for repeated measures showed no differential trajectory over time for any biomarker; its confidence intervals for the average postoperative effect were narrower (approximately ±10% for IL-18 and −9% to +15% for IL-18BP). The only exception was the leukocyte count, which was approximately 10% higher throughout the postoperative period in Group NP, without a differential trajectory shape. Conclusions: This pre-specified secondary analysis of a randomized trial found no evidence that pulsatile CPB reduces the early postoperative inflammatory or myocardial-injury response compared with non-pulsatile CPB for any of the eight biomarkers studied, apart from a modest difference in leukocyte count that did not survive correction for multiple comparisons. The confidence intervals obtained exclude only moderate-to-large between-group differences in IL-18 and IL-18BP; smaller true differences remain compatible with the data and cannot be ruled out at this sample size. These findings should not be interpreted as evidence of biochemical equivalence between pulsatile and non-pulsatile CPB, but they do not support a clinically important early anti-inflammatory advantage of pulsatile perfusion in this population.