Cardiac surgery necessitating cardiopulmonary bypass (snCPB) is often associated with the systemic inflammatory response syndrome (SIRS) and insufficient post-operative oxygenation, transiently fulfilling the criteria for acute lung injury (ALI); for a minority, SIRS becomes severe with an inherent mortality risk. SIRS is characterised by a marked increase in the production of neutrophils and their recruitment into the circulation. S100A12 (calgranulins C, EN-RAGE) is the predominant endogenously expressed neutrophil associated S100 protein. Its presence in plasma suggests utility as a biomarker of inflammation given that S100A12 was the first S100 protein shown to bind to the pro-inflammatory receptor for advanced glycation end-products (RAGE). We therefore undertook this study to ascertain whether increased release of S100A12 following snCPB is associated with aspects of the operative procedure and also levels of other established biomarkers of inflammation/ neutrophil activation in this patient population.
Methods 39 patients undergoing complex cardiac surgery necessitating CPB were recruited for the study. Peripheral blood was collected pre-operatively and immediately post-CPB and plasma was isolated. Enzyme-linked immunosorbent assays were used to measure myeloperoxidase (MPO), S100A12, IL-6 and IL-8 in these samples. In addition a series of clinical patient variables were recorded. Statistical analysis was performed using GraphPad Prism v.5, USA. One way ANOVA followed by post-hoc Dunn’s test was used and a p value of <0.05 was considered significant. Correlation between variables was assessed using the nonparametric Spearman test.
Results Plasma levels of S100A12 were significantly increased following snCPB (from 8.52 ng/ml, IQR 4.1–13.1 to 144.6 ng/ml, IQR 86.7–206.7). Post-snCPB levels of S100A12 correlated, positively with post-snCPB levels of MPO (r = 0.418, p = 0.01), white cell count (r = 0.322, p = 0.01) and neutrophil count (r = 0.363, p = 0.027), as well as CPB time (r = 0.399, p = 0.013), but not with length of ICU and hospital stay.
Conclusion The study shows that surgery-necessitating CPB results in the release of S100A12. Associations found suggest that S100A12 may be a biomarker for neutrophilia and neutrophil activation related to the onset of SIRS in this population.