Antioxidant Trace Element Reduction in an In Vitro Cardiopulmonary Bypass Circuit

Abstract

Many complications occurring after cardiac surgery are attributed to an acute increase in reactive oxygen and reactive nitrogen species, which under normal conditions are balanced by the antioxidant response. Two key enzymes of the antioxidant response, glutathione peroxidase (GPx) and superoxide dismutase (SOD), rely on trace elements for normal function. It was hypothesized that circulation of blood through the cardiopulmonary bypass (CPB) circuit would 1) reduce trace element levels and antioxidant function, 2) increase oxidative stress, and that 3) prepriming circuits with albumin would ameliorate trace element loss. This hypothesis was investigated by circulating fresh human whole blood in an in vitro CPB circuit. Plasma selenium, copper, and zinc levels were measured, as were SOD and GPx and oxidative stress by thiobarbituric acid reactive substances (TBARS). In spite of significant decreases in copper and zinc levels, SOD levels increased with time. Significant decreases in selenium were associated with a trend to increase TBARS but no change in GPx. Prepriming with albumin provided no benefit as it did not reduce trace element loss nor alter levels of oxidative stress. This study confirms that CPB circuits cause significant depletion of trace elements (selenium, copper, and zinc) necessary to maintain redox homeostasis. The loss of trace elements is a potential contributor to cardiac surgical morbidities, and further studies in the cardiac patient population are needed to investigate this.

Selenium and oxidative stress modulation during extracorporeal circulation

“…We have previously demonstrated that CPB circuits adsorb trace elements. 47 Given the similarities between CPB and ECMO circuits this presents another mechanism for the loss of trace elements such as selenium. In addition, because patients on ECMO are critically ill, the associated altered gut motility and absorption may compromise dietary intake of trace elements.…”

“…Intra-operatively the important triggers to oxidative stress are myocardial ischemia-reperfusion, 141 inflammation, 20 hyperoxia, 142 PRBC transfusion 57 and blood contact with the CPB circuit. 47 Levels of lipid peroxidation and protein carbonyl products are elevated in the myocardium, especially after ischemic reperfusion at the end of surgery. 51 Mitochondria, NAPH oxidase and uncoupled NOS are important sources of oxidative species in the myocardium at this time.…”

“…Specific RNOS triggering events in the critically ill, which are especially relevant to the ECMO patient, are listed in (Figure 2-4). Limited experimental data suggests that hyperoxia in this setting may facilitate neutrophil sequestration to the lungs, leading to increased pulmonary endothelial Sequestration of antioxidant trace elements by the ECMO circuit 47 RNOS production and lipid peroxidation. 54,67 Given the ability of these oxidative stress triggers to increase ECMO morbidity and mortality, it highlights the need for detailed oxidative stress studies in this cohort.…”

“…47,78,79 In addition to providing appropriate nutritional support in patients exposed to ECC, replacement of these antioxidant micronutrients may be a relatively low cost and safe intervention to mitigate the effects of oxidative stress. 78,80 Various compounds with antioxidant properties that have been investigated, either as individual supplements or in combination therapy, are discussed in brief below.…”

“…46 Concurrently, the ECC circuit adsorbs trace elements vital to the antioxidant response, specifically selenium and zinc. 47 Miniextracorporeal circuits (MECC) have a smaller surface area relative to standard CPB circuits. Select studies have shown reduced circulating levels of C-reactive protein (CRP), TNF and (interleukin-6) IL-6 when MECC are used in cardiac surgery.…”