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.

Keywords: anesthesia; cardiac surgery; endothelial dysfunction; endothelial glycocalyx; endothelium; intensive care.

Figure 1

Structure of endothelial glycoaylyx. Schematic representation of the basic structure of endothelial glycocalyx (EG) under normal physiologycal conditions. EG forms a protective layer of glycosaminoglycans, proteoglycans (syndecans, glypicans) and incorporated proteins on the luminal side of vascular endothelial cells, preventing direct contact of blood elements with the blood vessel wall. The components of EG transmit intraluminal events to endothelial cells activating the enzymes (protein kinase C) and intracellular signaling pathways. Abbreviations: Alb—albumin, BM—basement membrane, ChS—chondroitin sulphate, EG—endothelial glycocalyx, ESL—endothelial surphace layer, GLYP 1—glypican 1, GP—glycoprotein, HS—heparan sulphate, Orm—orosomucoid, PKC—protein kinase C, SA—sialic acid, SYN 1—syndecan 1, VEC—vascular endothelial cell.

Figure 2

Mechanisms of endothelial glycocalyx degradation (“shedding”). Any pathological situation, like trauma or ischemia/reperfusion injury, can lead to degradation of endothelial glycocalyx (EG). Shear stress activates inflammatory cells, which release highly reactive chemicals (ROS, RNS), cytokines, and proteaze enzymes. Consequently, the inhibition of endothelial nitric oxide synthase (eNOS) synthesis and protein kinase C (PKC) activity result in impared ability of vasodilatation and inhibition of intracellular signaling pathways, thus leading to EG degradation, dysfunction of endothelial cells’ regulatory functions, and leukocyte and platelet adhesion. Abbreviations: Alb—albumin, ChS—chondroitin sulphate, eNOS—endothelial nitric oxyde synthase, GLYP 1—glypican 1, GP—glycoprotein, HPSE—heparanase, HS—heparan sulphate, IL-1—interleukin-1, IL-6—interleukin-6, MMP—matrix metaloproteinase, Orm—orosomucoid, PKC—protein kinase C, RNS—reactive nitrogen species, ROS—reactive oxygen species, SA—sialic acid, SYN 1—syndecan 1, TNF- α—tumor necrosis factor alpha.