Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Pharmacology, Department of General Pharmacology, University Medicine Greifswald, Greifswald, Germany.
Front Immunol. 2021 Oct 20;12:761475. doi: 10.3389/fimmu.2021.761475. eCollection 2021.
Sphingosine-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.
In 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.
Median 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.
In 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.
鞘氨醇-1-磷酸（S1P）是一种信号脂质，在血管保护和免疫反应中至关重要。S1P 介导的过程涉及内皮屏障的调节、血压和 S1P 是唯一已知的淋巴细胞迁移诱导剂。循环 S1P 水平低与严重的全身炎症综合征如败血症和休克状态相关，这些综合征与内皮屏障破坏和免疫抑制有关。我们研究了心脏手术引起的无菌性炎症是否会影响 S1P 水平。
在这项前瞻性观察研究中，我们纳入了 46 名接受心脏手术的患者，其中体外循环（CPB，n=31）和非体外循环（非 CPB，n=15）。在基线、手术后以及手术后第 1 天（POD 1）和第 4 天（POD 4）测量血清-S1P、S1P 来源和载体、血管性血友病因子（vWF）、C 反应蛋白（CRP）、降钙素原（PCT）和白细胞介素-6（IL-6）。
基线时 S1P 中位数为 0.77 nmol/mL（IQR 0.61-0.99），手术后显著下降。CPB 后 S1P 最低，中位数水平为 0.37 nmol/mL（IQR 0.31-0.47），非 CPB 后为 0.46 nmol/mL（IQR 0.36-0.51）（P<0.001）。S1P 的下降与手术技术无关，并且在所有个体中均观察到。在 S1P 水平未恢复到术前基线的患者中，ICU 停留时间更长，术后炎症更严重。S1P 水平与 S1P 的来源和载体以及 vWF 相关，vWF 是一种更特异的内皮损伤标志物，在术后不同阶段。术中 S1P 水平的测定表明，肝素的抗凝作用也可能影响全身 S1P。
总之，心脏大手术后血清 S1P 水平受到干扰。术后 S1P 水平低可能作为心脏手术引起炎症严重程度的新标志物发挥作用。由于 S1P 具有众所周知的保护作用，低 S1P 水平可能进一步导致观察到的 ICU 停留时间延长和临床状况恶化。此外，我们不能排除肝素抗凝在手术期间对循环 S1P 水平的潜在抑制作用，这将是心脏手术患者中肝素高剂量的一种新的促炎多效性作用。
