Dynamics of Vascular Protective and Immune Supportive Sphingosine-1-Phosphate During Cardiac Surgery

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.

Nomogram predicts atrial fibrillation after coronary artery bypass grafting

“…Studies have shown that the operative time is associated with POAF, and a longer operative time may lead to more severe atrial ischemia and inflammation, which is more likely to induce POAF [ 18 ]. Off-pump theoretically reduces the inflammatory response and myocardial injury in patients [ 19 ], and this opinion was confirmed by Fan et al[ 14 ] In this study, the usage rate of cardiopulmonary bypass in POAF group is higher than non-POAF group (11.3% v.s. 8.5%).However, there was no significant difference between the two groups.…”

Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy

“…Subtype 1 (S1P1) is required in the protection of endothelial barrier function, whereas the activation of S1P2 and S1P3 receptors disrupts the endothelial barrier. Pharmacological activation of the S1P1 receptor with FTY-720 and SEW2871 preserved vascular function in rats on CPB [238] and might be an interesting target to protect both the vasculature and the heart as low circulating levels of S1P were found in cardiac surgery patients [239].…”