未经证实:心脏手术和体外循环的使用会引发全身炎症反应。无翼相关整合位点(WNT)信号是先天免疫的一部分,在炎症调节中起着重要作用。在临床前研究中,WNT-5a可维持炎症反应并引起内皮功能障碍。我们的目的是调查心脏手术后的WNT信号及其与术后炎症的关系(Clinicaltrials.gov,NCT04058496)。
未经批准:在此前瞻性中,单中心,观察性研究,64例冠状动脉旁路移植术(CABG)±瓣膜手术的连续患者被分为三组:非体外循环CABG(n=28),泵上CABG(n=16)和联合瓣膜-CABG手术(n=20)。手术前采集血样,在重症监护病房(ICU)入院时以及此后的4、8和48小时。WNT-5a及其拮抗剂的血浆浓度分泌型卷曲相关蛋白1(sFRP-1),分泌型卷曲相关蛋白5(sFRP-5),酶联免疫吸附法测定WNT抑制因子1(WIF-1)。此外,采用多重免疫分析法检测血浆中6种炎性细胞因子的浓度。分析血浆浓度随时间变化的参数,互动,组间差异,并与临床结果参数相关。
未经评估:在基线时,WNT-5a,sFRP-1和WIF-1以最低浓度存在,而sFRP-5升高。WNT-5a的基线值越高,sFRP-5和WIF-1导致相应参数的更高的后续值。入住ICU时,WNT-5a和sFRP-5达到最大值和最小值,分别。WIF-1随时间下降,术后8小时最低。sFRP-1随时间变化最小。当WNT-5a在48小时内恢复到基线时,sFRP-5和WIF-1在48小时未达到其基线值。在所研究的WNT系统组件中,只有WIF-1部分反映了手术的严重程度.WNT-5a和WIF-1对术后体液平衡和去甲肾上腺素需求有影响。
未经批准:WNT-5a,sFRP-5和WIF-1是心脏手术后全身炎症反应的一部分。WNT-5a在心脏手术后立即达到峰值,并在48小时内恢复到基线,推测受其拮抗剂sFRP-5调节。基于这项翻译研究,可以进一步研究WNT-5a拮抗作用,以评估心脏手术后炎症失调的患者的潜在有益作用。
UNASSIGNED: Cardiac surgery and the use of cardiopulmonary bypass initiate a systemic inflammatory response. Wingless-related integration site (WNT) signaling is part of the innate immunity and has been attributed a major role in the regulation of inflammation. In preclinical research, WNT-5a may sustain an inflammatory response and cause endothelial dysfunction. Our aim was to investigate WNT signaling after cardiac surgery and its association with postoperative inflammation (Clinicaltrials.gov, NCT04058496).
UNASSIGNED: In this prospective, single-center, observational
study, 64 consecutive patients for coronary artery bypass grafting (CABG) ± valve surgery were assigned into three groups: off-pump CABG (n = 28), on-pump CABG (n = 16) and combined valve-CABG surgery (n = 20). Blood samples were acquired before surgery, at intensive care unit (ICU) admission and 4, 8, and 48 h thereafter. Plasma concentrations of WNT-5a and its antagonists Secreted frizzled-related protein 1 (sFRP-1), Secreted frizzled-related protein 5 (sFRP-5), and WNT inhibitory factor 1 (WIF-1) were determined by enzyme-linked immunosorbent assay. In addition, plasma concentrations of six inflammatory cytokines were measured by multiplex immunoassay. Parameters were analyzed for evolution of plasma concentration over time, interactions, intergroup differences, and association with clinical outcome parameters.
UNASSIGNED: At baseline, WNT-5a, sFRP-1, and WIF-1 were present in a minimal concentration, while sFRP-5 was elevated. A higher baseline value of WNT-5a, sFRP-5, and WIF-1 resulted in higher subsequent values of the respective parameter. At ICU admission, WNT-5a and sFRP-5 reached their maximum and minimum value, respectively. WIF-1 decreased over time and was lowest 8 h after surgery. sFRP-1 changed minimally over time. While WNT-5a returned to the baseline within 48 h, sFRP-5 and WIF-1 did not reach their baseline value at 48 h. Of the investigated WNT system components, only WIF-1 partially reflected the severity of surgery. WNT-5a and WIF-1 had an impact on postoperative fluid balance and noradrenaline requirement.
UNASSIGNED: WNT-5a, sFRP-5, and WIF-1 are part of the systemic inflammatory response after cardiac surgery. WNT-5a peaks immediately after cardiac surgery and returns to baseline within 48 h, presumably modulated by its antagonist sFRP-5. Based on this translational
study, WNT-5a antagonism may be further investigated to assess potentially beneficial effects in patients with a dysregulated inflammation after cardiac surgery.