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.

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: Intraoperative fluid management is a crucial aspect of cancer surgery, including colorectal surgery and pancreatoduodenectomy. The study tests if intraoperative multimodal monitoring reduces postoperative morbidity and duration of hospitalisation in patients undergoing major abdominal surgery treated by the same anaesthetic protocols with epidural analgesia. Patients and methods: A prospective study was conducted in 2 parallel groups. High-risk surgical patients undergoing major abdominal surgery were randomly selected in the control group (CG), where standard monitoring was applied (44 patients), and the protocol group (PG), where cerebral oxygenation and extended hemodynamic monitoring were used with the protocol for intraoperative interventions (44 patients). Results: There were no differences in the median length of hospital stay, CG 9 days (interquartile range [IQR] 8 days), PG 9 (5.5), p = 0.851. There was no difference in postoperative renal of cardiac impairment. Procalcitonin was significantly higher (highest postoperative value in the first 3 days) in CG, 0.75 mcg/L (IQR 3.19 mcg/L), than in PG, 0.3 mcg/L (0.88 mcg/L), p = 0.001. PG patients received a larger volume of intraoperative fluid; median intraoperative fluid balance +1300 ml (IQR 1063 ml) than CG; +375 ml (IQR 438 ml), p < 0.001. Conclusions: There were significant differences in intraoperative fluid management and vasopressor use. The median postoperative value of procalcitonin was significantly higher in CG, suggesting differences in immune response to tissue trauma in different intraoperative fluid status, but there was no difference in postoperative morbidity or hospital stay.

Neurocognitive decline during the perioperative period represents a risk of significant complications, including dementia and death. The aim of our study was to observe the change in biomarkers of neuroinflammation in optimized anesthesia without clinical signs of perioperative neurocognitive decline. Observational study included high-risk surgical patients who underwent large intestinal resections. Balanced anaesthesia was used to maximize cerebral protection. The release of NSE, protein S-100, matrix metalloproteinase-9 (MMP-9) and other biomarkers of cerebral injury were measured in serum samples using immunochemical methods during and after surgery. Profiles of proteins MMP-9 and S-100 showed perioperative increase, which was in accordance with intraoperative cerebral injury. Despite the increase, the S-100 and NSE plasma levels remained within normal range. The study highlights the perioperative expression of proteins MMP-9 and S-100, which might be useful as biomarkers of cerebral injury in the context of balanced anesthesia during major abdominal surgery.

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.