Abstract
IntroductionSphingosine-1-phosphate (S1P) is a signaling lipid and crucial in vascular protection and immune response. S1P mediated processes involve regulation of the endothelial barrier, blood pressure and S1P is the only known inducer of lymphocyte migration. Low levels of circulatory S1P correlate with severe systemic inflammatory syndromes such as sepsis and shock states, which are associated with endothelial barrier breakdown and immunosuppression. We investigated whether S1P levels are affected by sterile inflammation induced by cardiac surgery.Materials and MethodsIn this prospective observational study we included 46 cardiac surgery patients, with cardiopulmonary bypass (CPB, n=31) and without CPB (off-pump, n=15). Serum-S1P, S1P-sources and carriers, von-Willebrand factor (vWF), C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) were measured at baseline, post-surgery and at day 1 (POD 1) and day 4 (POD 4) after surgical stimulus.ResultsMedian S1P levels at baseline were 0.77 nmol/mL (IQR 0.61-0.99) and dropped significantly post-surgery. S1P was lowest post-surgery with median levels of 0.37 nmol/mL (IQR 0.31-0.47) after CPB and 0.46 nmol/mL (IQR 0.36-0.51) after off-pump procedures (P<0.001). The decrease of S1P was independent of surgical technique and observed in all individuals. In patients, in which S1P levels did not recover to preoperative baseline ICU stay was longer and postoperative inflammation was more severe. S1P levels are associated with its sources and carriers and vWF, as a more specific endothelial injury marker, in different phases of the postoperative course. Determination of S1P levels during surgery suggested that also the anticoagulative effect of heparin might influence systemic S1P.DiscussionIn summary, serum-S1P levels are disrupted by major cardiac surgery. Low S1P levels post-surgery may play a role as a new marker for severity of cardiac surgery induced inflammation. Due to well-known protective effects of S1P, low S1P levels may further contribute to the observed prolonged ICU stay and worse clinical status. Moreover, we cannot exclude a potential inhibitory effect on circulating S1P levels by heparin anticoagulation during surgery, which would be a new pro-inflammatory pleiotropic effect of high dose heparin in patients undergoing cardiac surgery.
Highlights
Sphingosine-1-phosphate (S1P) is a signaling lipid and crucial in vascular protection and immune response
All other markers showed a contrary trend with significant peak levels either directly post-surgery, on postoperative day (POD) 1, or POD4
The resulting systemic inflammatory response is associated with severe intra- and postoperative complications as myocardial, respiratory and acute kidney injury (AKI), neurological impairment, bleeding and in its most severe form multiorgan failure [27]
Summary
Sphingosine-1-phosphate (S1P) is a signaling lipid and crucial in vascular protection and immune response. Surgery related mortality has partially been attributed to the surgery induced acute inflammatory response In this context, cardiopulmonary bypass (CPB) induces severe inflammation and is associated with higher risk of organ failure such as acute kidney injury (AKI), which increases the risk of not surviving the hospital stay by 2-fold [3,4,5]. Hallmarks are hypotension caused by vasoplegia, edema formation caused by endothelial barrier disruption and uncontrolled cytokine secretion with an increased vulnerability for secondary infections All of these processes are potentially regulated by the vascular protective G-protein coupled signalling lipid sphingosine-1-phosphate (S1P) [9]. S1P signaling may depend on its main carrier, highdensity lipoprotein (HDL) or albumin [18]
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