The Crucial Triad: Endothelial Glycocalyx, Oxidative Stress, and Inflammation in Cardiac Surgery-Exploring the Molecular Connections

Abstract

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.

Keywords: cardiac surgery; endothelial dysfunction; endothelial glycocalyx; endothelium; inflammation; oxidative stress.

Figure 1

Schematic representation of the endothelial glycocalyx (EG) structure under physiological conditions. The EG covers the luminal surface of blood vessels. Some elements (glycoprotein, syndecan, and glypican) are bound to endothelial cells, while others (like heparan sulphate and chondroitin sulphate) have an indirect connection. Some molecules (like orosomucoid and albumins) are “trapped” within the matrix molecules. (ORM—orosomucoid).

Figure 2

Schematic representation of EG exposed to shear stress. Note the detachment of heparan and chondroitin sulphate. Various proteases (primary matrix metalloproteinases (MMP), heparanase, and hyaluronidase) are released by activated leukocytes or induced by mechanical stress. Proteases cleave the core proteins of proteoglycans and glycoproteins in the endothelial glycocalyx, leading to their degradation. (ORM—orosomucoid).

Figure 3

Inflammatory response in heart damage. This Figure represents the autophagy process in response to cardiac injury, such as ischemia, sepsis, or ischemia–reperfusion injury. Following cardiac injury, an inflammatory response is triggered, which activates the autophagy pathway. Damaged cells, including apoptotic cells, viruses, bacteria, damage-associated molecular patterns (DAMPs), and damaged mitochondria, are encapsulated in a double-membrane structure called an autophagosome. LC3-II is a marker protein involved in the formation of the autophagosome. The autophagosome then fuses with a lysosome, forming an autolysosome. The lysosomal enzymes degrade the encapsulated cell debris within the autolysosome, leading to its breakdown and recycling, thereby aiding cellular recovery and homeostasis.