Endothelial Dysfunction in Patients Undergoing Cardiac Surgery: A Narrative Review and Clinical Implications

Abstract

Cardiac surgery is one of the highest-risk procedures, usually involving cardiopulmonary bypass and commonly inducing endothelial injury that contributes to the development of perioperative and postoperative organ dysfunction. Substantial scientific efforts are being made to unravel the complex interaction of biomolecules involved in endothelial dysfunction to find new therapeutic targets and biomarkers and to develop therapeutic strategies to protect and restore the endothelium. This review highlights the current state-of-the-art knowledge on the structure and function of the endothelial glycocalyx and mechanisms of endothelial glycocalyx shedding in cardiac surgery. Particular emphasis is placed on potential strategies to protect and restore the endothelial glycocalyx in cardiac surgery. In addition, we have summarized and elaborated the latest evidence on conventional and potential biomarkers of endothelial dysfunction to provide a comprehensive synthesis of crucial mechanisms of endothelial dysfunction in patients undergoing cardiac surgery, and to highlight their clinical implications.

Insights into the Molecular Mechanism of Endothelial Glycocalyx Dysfunction during Heart Surgery

“…For valvular heart disease or for valve repair or replacement, open cardiac surgery may be necessary depending on the damaged valve [57]. If invasive cardiological therapy is not effective for a patient with severe ischemic heart disease, cardiac surgery is recommended [58]. Treatment strategies may involve open or less invasive procedures [59,60].…”

“…Roller and centrifugal pumps are common components of CPB machines, which offer non-pulsatile flow [14]. While pulsatile flow is recommended in adult open-heart surgery by the 2019 EACTS/EACTAIC/EBCP guidelines, the evidence for its superiority over non-pulsatile flow remains unclear, although pulsatile flow is a more natural option [56,58].…”

“…The shedding of glycosaminoglycans from EGC facilitates the release of chemokines and proinflammatory cytokines embedded in the EGC into the circulation [66][67][68]. In turn, the proinflammatory cytokines further promote glycocalyx shedding [58,69,70]. Cytokines support the stimulation of lymphocytes, activate complement, and produce reactive oxygen species (ROS) and reactive nitrogen species (RNS), which additionally damage endothelial cells [5,65].…”

“…Despite this limitation, circulating endothelial cells are able to stimulate these T cells to produce cytokines. This highlights a potential role for endothelial cells in immune regulation through cytokine signaling despite their inability to fully activate T cell proliferation and differentiation [58,[72][73][74].…”

Glycocalyx–Sodium Interaction in Vascular Endothelium

“…An intact glycocalyx is also essential for the normal structure or function of endothelial cells, and endothelial dysfunction is mainly associated with old age, as well as pathological conditions including inflammatory conditions, atherosclerosis, hypertension, and heart failure [ 14 ]. The extensive sulfation of the glycosaminoglycan (GAG) chains among the proteoglycans within the endothelial glycocalyx increases its negativity that allows it to bind plasma proteins such as albumin [ 15 ]. The major components of the endothelial glycocalyx that project into the vascular lumen are also involved in flow-mediated “mechanosensation-mechanotranduction” that affects nitric oxide synthesis and vasodilation [ 16 ].…”