Endothelial dysfunction, inflammation and oxidative stress in patients undergoing cardiac surgery

Cardiac surgery is a high-risk procedure commonly performed with cardiopulmonary bypass (CPB) which is associated with disturbances in microcirculation. This microcirculatory alteration can lead to development of perioperative complications such as decreased tissue perfusion and consequent hypoxia with postoperative organ dysfunction which can complicate the course of patient’s recovery. Cardiac surgery induces inflammation, ischemia-reperfusion injury and acute trauma that contribute to endothelial dysfunction. Vascular endothelium is involved in the inflammatory response to cardiac surgery and recently emerged as a scientific and clinical priority. The luminal surface of vascular endothelium is covered with glycocalyx, a multimolecular gel-like layer lining. It has an important physiologic role in maintaining vascular tone and permeability, mechanosensation, mechano-transduction, interaction between the blood and endothelial cells, nitric oxide signaling, scavenging oxygen free radicals and fluid homeostasis. The endothelial glycocalyx is a dynamic structure with a tenuous balance between degradation and synthesis. Under pathological conditions or trauma, such as cardiac surgery, inflammatory response is induced which can adversely affect this balance. Increased concentration of endothelial glycocalyx degradation markers such as syndecan-1, heparan sulphate or hyaluronic acid are associated with organ dysfunction and poor outcome in critically ill patients. Ischemia-reperfusion injury, CPB, fluid overload or hypovolemia during cardiac surgery can contribute to degradation of endothelial glycocalyx. The quantification of degraded endothelial glycocalyx components can serve as a prediction biomarker for estimating the degree of endothelial degradation and possible organ dysfunction. Although CPB remains a non-physiological procedure, it is widely accepted as a safe and effective method for open heart surgery when heart and lung must be excluded from the circulation to facilitate the surgical procedure. One of the most non-physiological features of CPB is the non-pulsatile flow generated by the pump in the extracorporeal circulation device. Recent evidence suggest that pulsatile CPB might be more physiological because it mimics vascular shear stress but the role of pulsatile versus non-pulsatile CPB is still far from being completely understood. The proposed project aims to investigate the difference between non-pulsatile and pulsatile CPB on endothelial dysfunction, oxidative stress and inflammatory response in patients undergoing aortic valvular replacement or coronary artery bypass grafting during surgery and in early postoperative period. The changes of endothelial glycocalyx, degree of oxidative stress and magnification of proinflammatory response will be correlated with anesthesia and surgical management and occurrence of organ dysfunction as well as patients’ recovery and outcome. Dynamic changes of endothelial glycocalyx will be acquired and analysed clinically and paraclinically to find qualitative and quantitative biomarkers that could be useful for prediction of patient’s course of recovery following cardiac surgery.