Division of Cardiac Surgery, Dalhousie University, Halifax, Canada.
Department of Clinical Perfusion, Nova Scotia Health Authority, Halifax, Canada.
J Transl Med. 2023 Jul 5;21(1):439. doi: 10.1186/s12967-023-04255-8.
Cardiopulmonary bypass (CPB) is associated with systemic inflammation, featuring increased levels of circulating pro-inflammatory cytokines. Intra-operative ultrafiltration extracts fluid and inflammatory factors potentially dampening inflammation-related organ dysfunction and enhancing post-operative recovery. This study aimed to define the impact of continuous subzero-balance ultrafiltration (SBUF) on circulating levels of major inflammatory mediators.
Twenty pediatric patients undergoing cardiac surgery, CPB and SBUF were prospectively enrolled. Blood samples were collected prior to CPB initiation (Pre-CPB Plasma) and immediately before weaning off CPB (End-CPB Plasma). Ultrafiltrate effluent samples were also collected at the End-CPB time-point (End-CPB Effluent). The concentrations of thirty-nine inflammatory factors were assessed and sieving coefficients were calculated.
A profound increase in inflammatory cytokines and activated complement products were noted in plasma following CBP. Twenty-two inflammatory mediators were detected in the ultrafiltrate effluent. Novel mediators removed by ultrafiltration included cytokines IL1-Ra, IL-2, IL-12, IL-17A, IL-33, TRAIL, GM-CSF, ET-1, and the chemokines CCL2, CCL3, CCL4, CXCL1, CXCL2 and CXCL10. Mediator extraction by SBUF was significantly associated with molecular mass < 66 kDa (Chi statistic = 18.8, Chi with Yates' correction = 16.0, p < 0.0001). There was a moderate negative linear correlation between molecular mass and sieving coefficient (Spearman R = - 0.45 and p = 0.02). Notably, the anti-inflammatory cytokine IL-10 was not efficiently extracted by SBUF.
CPB is associated with a burden of circulating inflammatory mediators, and SBUF selectively extracts twenty of these pro-inflammatory factors while preserving the key anti-inflammatory regulator IL-10. Ultrafiltration could potentially function as an immunomodulatory therapy during pediatric cardiac surgery. Trial registration ClinicalTrials.gov, NCT05154864. Registered retrospectively on December 13, 2021. https://clinicaltrials.gov/ct2/show/record/NCT05154864 .
体外循环（CPB）与全身炎症有关，表现为循环中促炎细胞因子水平升高。术中超滤提取液体和炎症因子，可能减轻炎症相关的器官功能障碍，促进术后恢复。本研究旨在确定持续亚零平衡超滤（SBUF）对循环中主要炎症介质的影响。
前瞻性纳入 20 例接受心脏手术、CPB 和 SBUF 的儿科患者。在 CPB 开始前（CPB 前血浆）和即将脱机 CPB 时（CPB 结束时血浆）采集血样。CPB 结束时还采集超滤流出液样本（CPB 结束时流出液）。评估了 39 种炎症因子的浓度，并计算了筛系数。
CPB 后血浆中炎症细胞因子和激活的补体产物明显增加。超滤流出液中检测到 22 种炎症介质。超滤去除的新型介质包括细胞因子 IL1-Ra、IL-2、IL-12、IL-17A、IL-33、TRAIL、GM-CSF、ET-1 和趋化因子 CCL2、CCL3、CCL4、CXCL1、CXCL2 和 CXCL10。SBUF 对介质的提取与分子量 < 66 kDa 显著相关（卡方检验= 18.8，卡方检验校正 Yates 后= 16.0，p < 0.0001）。分子量与筛系数呈中度负线性相关（Spearman R= -0.45，p= 0.02）。值得注意的是，抗炎细胞因子 IL-10 不能被 SBUF 有效提取。
CPB 与循环中炎症介质负担有关，SBUF 选择性提取其中 20 种促炎因子，同时保留关键抗炎调节剂 IL-10。超滤术可能在儿科心脏手术中作为一种免疫调节治疗。
ClinicalTrials.gov，NCT05154864。2021 年 12 月 13 日回顾性注册。https://clinicaltrials.gov/ct2/show/record/NCT05154864。
