Selenium and oxidative stress modulation during extracorporeal circulation

Abstract

Oxidative stress occurs when there is an imbalance between reactive oxygen and nitrogen species (RNOS) and the antioxidant system. In cardiac surgery patients and the critically ill there is an association between oxidative stress and morbidity and mortality.Extracorporeal circulation (ECC) encompasses cardiopulmonary bypass (CPB) which is used for cardiac surgery; extracorporeal membrane oxygenation (ECMO) which is used for cardio-respiratory support in the critically ill and haemodialysis which is used in patients with intermittent or end-stage renal failure.During ECC, the patient's total blood volume is in direct contact with an artificial surface for extended periods. In addition, there is often pre-existing inflammation, surgical trauma and/or ischemia-reperfusion (I-R) injury, all of which are major activators for the increased production of RNOS. Concurrent decreases in the level of essential antioxidants and trace elements (such as selenium, zinc and copper) occur, which upset redox balance in favour of oxidative stress. The trace element selenium is required for the normal function of the antioxidant enzyme glutathione peroxidase (GPx). Despite in vitro and biochemical data suggesting that reinforcement of antioxidant activity by selenium supplementation might reduce excessive oxidative stress damage, there is conflicting evidence in clinical studies.The reason for failure of antioxidant supplementation in the clinical setting is currently unclear.We postulated that the ECC and its associated interventions such as transfusion, might have a larger impact on trace element loss, antioxidant function and the oxidative stress response than previously recognised. This led to the following questions:  What is the selenium level in healthy Queensland residents, and is this level similar to that reported in other parts of the world? Does a patient's pre-CPB or pre-ECMO circulating selenium level influence their outcome? Does the ECC independently alter circulating selenium levels and the oxidative stress response? Do other interventions during ECC, such as transfusion, alter circulating selenium and oxidative stress levels?iii This thesis focussed on oxidative stress and the trace element selenium, because oxidative stress is associated with poorer outcomes in cardiac and critically ill patients, and decreased selenium is independently associated with poorer outcomes. To answer the research questions outlined above, a series of experiments were designed and conducted, and they generated the following new information.The average selenium level in a Queensland blood donor population was defined at 1.09 µmol/L (Chapter 3). In addition 88.5% of participants had a selenium level lower than the critical level required for maximal glutathione peroxidase activity, which has previously been determined to be between 1.14 -1.27 µmol/L. Furthermore, this study generated novel information that packed red blood cells and buffy coat pooled platelets have very low levels of selenium (≤ 0.3 µmol/L).The effect of car...

Effect of Selenium Added to the Cardioplegic Solution on Cardiac Protection in Coronary Artery Bypass Grafting Surgeries: A Randomized, Double-Blinded, Clinical Trial Study

“…Also, selenium deficiency may be involved in the development and progression of CVDs, possibly by 1-increasing thromboxane B2 synthesis, which subsequently leads to platelet aggregation and 2-decreasing prostacyclin production, which inhibits platelet aggregation (12). The level of selenium dramatically declines following heart surgeries and dialysis (13), resulting in unwanted complications and morbidities in both conditions (14,15). A previous study also indicated a reduction in selenium level in patients under CABG surgery (14).…”