Pino C J, Lou L, Smith P L, Ding F, Pagani F D, Buffington D A, Humes H D
Innovative BioTherapies Inc., Ann Arbor, MI 48108, USA.
Perfusion. 2012 Jul;27(4):311-9. doi: 10.1177/0267659112444944. Epub 2012 Apr 16.
Systemic inflammatory response syndrome (SIRS) can occur in association with cardiopulmonary bypass (CPB) surgery, resulting in multiple organ dysfunction (MOD). Activated neutrophils have been implicated as major inciting factors in this process. Neutrophil-depleting filters incorporated within the extracorporeal blood circuit during CPB have been developed and evaluated, with inconsistent clinical results.
A novel, biomimetic, selective cytopheretic device (SCD) was tested in vitro within a blood circuit to assess safety and interactions with blood components and further evaluated ex vivo in a bovine model of CPB surgery during ventricular assist device implantation.
In vitro blood circuit studies demonstrated that the SCD reduces circulating neutrophils while maintaining low rates of hemolysis compared to current leukocyte-reduction filters. In the bovine CPB model, animals without SCD treatment (No SCD) demonstrated an increase in circulating white blood cell (WBC) and neutrophil counts, steadily increasing throughout CPB. SCD with only systemic heparin anticoagulation (SCD-H) acutely reduced neutrophils for the first 2 hrs of CPB, but followed with a greater than 6-fold increase in neutrophil counts. SCD treatment with regional citrate anticoagulation along the SCD circuit (SCD-C) reduced systemic neutrophil counts throughout 4 hrs of CPB despite lower amounts of eluted cells from the SCD. When analyzed for immature neutrophils, the control and SCD-H showed increasing counts at later time-points, not seen in the SCD-C group, suggesting a more complex mechanism of action than simple leukoreduction.
These results suggest that SCD-C therapy may disrupt the systemic leukocyte response during CPB, leading to improved outcomes for CPB-mediated MOD.
全身炎症反应综合征（SIRS）可与体外循环（CPB）手术相关联发生，导致多器官功能障碍（MOD）。活化的中性粒细胞被认为是这一过程中的主要激发因素。在CPB期间，已开发并评估了体外血液回路中包含的中性粒细胞清除滤器，但临床结果不一致。
一种新型的、仿生的、选择性细胞去除装置（SCD）在体外血液回路中进行了测试，以评估其安全性以及与血液成分的相互作用，并在心室辅助装置植入期间的CPB牛模型中进行了离体进一步评估。
体外血液回路研究表明，与目前的白细胞去除滤器相比，SCD可减少循环中的中性粒细胞，同时保持较低的溶血率。在牛CPB模型中，未经SCD治疗的动物（无SCD）循环白细胞（WBC）和中性粒细胞计数增加，在整个CPB过程中持续上升。仅采用全身肝素抗凝的SCD（SCD-H）在CPB的前2小时急性减少了中性粒细胞，但随后中性粒细胞计数增加了6倍以上。沿SCD回路采用局部枸橼酸盐抗凝的SCD治疗（SCD-C）在整个4小时的CPB过程中降低了全身中性粒细胞计数，尽管从SCD洗脱的细胞数量较少。在分析未成熟中性粒细胞时，对照组和SCD-H在后期时间点显示计数增加，而SCD-C组未出现这种情况，这表明其作用机制比单纯的白细胞去除更为复杂。
这些结果表明，SCD-C疗法可能会破坏CPB期间的全身白细胞反应，从而改善CPB介导的MOD的预后。
