Abstract
Background. The receptor for advanced glycation end products (RAGE) is an inflammation-perpetuating receptor, and soluble RAGE (sRAGE) is a marker of cellular RAGE expression. This study investigated whether raised plasma levels prior to surgery of sRAGE or S100A8/A9 (a RAGE ligand) were associated with longer duration of hospital care in patients undergoing cardiac surgery necessitating cardiopulmonary bypass. Methods. Patients (n = 130) undergoing elective cardiac surgery were enrolled prospectively. Plasma sRAGE and S100A8/A9 concentrations were measured before and 2 h after surgery. Results. Preoperative plasma sRAGE increased significantly (P < 0.0001) from 1.06 ng/mL (IQR, 0.72–1.76) to 1.93 ng/mL (IQR, 1.14–2.63) 2 h postoperatively. Plasma S100A8/9 was also significantly (P < 0.0001) higher 2 h postoperatively (2.37 μg/mL, IQR, 1.81–3.05) compared to pre-operative levels (0.41 μg/mL, IQR, 0.2–0.65). Preoperative sRAGE, but not S100A8/A9, was positively and significantly correlated with duration of critical illness (r = 0.3, P = 0.0007) and length of hospital stay (LOS; r = 0.31, P < 0.0005). Multivariate binary logistic regression showed preoperative sRAGE to be, statistically, an independent predictor of greater than median duration of critical illness (odds ratio 16.6, P = 0.014) and to be, statistically, the strongest independent predictor of hospital LOS. Conclusion. Higher preoperative plasma sRAGE levels were associated with prolonged duration of care in adults undergoing cardiac surgery requiring cardiopulmonary bypass.
Highlights
First described as a receptor (R) for advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE) is an immunoglobulin-like pattern recognition receptor constitutively expressed at low levels in all cells and at high levels in the lung [1, 2]
This study has shown that plasma levels of soluble RAGE (sRAGE) and S100A8/9 were raised postoperatively in patients after snCPB
Preoperative sRAGE was the only variable, when duration was categorised as greater or less than the median, with an independent relationship to duration of level care 3 and, statistically, the strongest predictor of hospital length of hospital stay (LOS). These novel findings suggest that higher preoperative plasma sRAGE levels are indicative of longer recovery after cardiac surgery requiring cardiopulmonary bypass (CPB), suggesting increased RAGE activation prior to surgery is not advantageous
Summary
First described as a receptor (R) for advanced glycation end products (AGEs), RAGE is an immunoglobulin-like pattern recognition receptor constitutively expressed at low levels in all cells and at high levels in the lung [1, 2]. A “two-hit” model describes the role of RAGE in inflammation which hypothesizes that chronic conditions such as renal failure or diabetes and increasing age per se [9], some of the preoperative risks factors for cardiac surgery, represent a first inflammatory “hit,” leading to widespread upregulation of RAGE expression [1]. A second, superimposed acute inflammatory insult, such as cardiac surgery necessitating (sn) cardiopulmonary bypass (CPB) or Mediators of Inflammation other conditions associated with hyperglycaemia, ischaemic stress, and release of inflammatory mediators, leads to a further increase of RAGE ligands [1]. This study investigated whether raised plasma levels prior to surgery of sRAGE or S100A8/A9 (a RAGE ligand) were associated with longer duration of hospital care in patients undergoing cardiac surgery necessitating cardiopulmonary bypass. Higher preoperative plasma sRAGE levels were associated with prolonged duration of care in adults undergoing cardiac surgery requiring cardiopulmonary bypass
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