A selective cytopheretic inhibitory device for use during cardiopulmonary bypass surgery

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: These results suggest that SCD-C therapy may disrupt the systemic leukocyte response during CPB, leading to improved outcomes for CPB-mediated MOD.