title: Red blood cell aggregation during cardiopulmonary bypass: a pathogenic cofactor in endothelial cell activation?
abstract: OBJECTIVE
  The bio-incompatibility of the cardiopulmonary bypass (CPB) circuit and the use of artificial colloids trigger massive defense reaction that involves endothelial cells and several blood cells: platelets, neutrophils, monocytes, red blood cells (RBC) and lymphocytes. Investigating the effects on RBC aggregation and endothelial cells activation, the present study addresses two different prime solutions commonly used in the clinical practice.
  
  
  METHODS
  RBC aggregation was measured by means of Laser-assisted Optical Rotation Cell Analyzer, in an in vitro study designed to mimic the human blood-material interactions during extracorporeal circulation. A clinical study investigating endothelial activation was conducted in 20 patients undergoing elective coronary bypass surgery, randomly assigned for CPB using two different priming solutions: HAES-steril 6% (HES 200/0.5) and Voluven 6% (HES 130/0.4).
  
  
  RESULTS
  Circulation trough a Chandler loop of HES-blood mixes altered significantly RBC aggregability. The use of HES 130/0.4 resulted in marked decrease in RBC aggregation (aggregation index (AI) before and after circulation was 23.5+/-3.8 and 18+/-2.9, respectively), no significant differences being found when compared with Ringer's lactate group. The use of HES 200/0.5 resulted in better maintained RBC aggregation (AI 39.7+/-5.9 and 29.7+/-4.7 before and after circulation, respectively). The AI measured for the whole blood (control) sample was 61.9+/-4.9 before circulation, and 58.1+/-4 after. Markers of endothelial activation (von Willebrand factor (vWF), thrombomodulin (TM), tissue plasminogen activator (tPA) and E-selectin) significantly increased during CPB. Differences between HES treatment groups were evident post-bypass. While the markers of endothelial activation returned to baseline in HES 200/0.5 group, HES 130/0.4 was associated on the first post-operative day with further increase of vWF and tPA.
  
  
  CONCLUSIONS
  RBC aggregation significantly drooped as consequence of blood dilution and blood-material interaction. We reason that low RBC aggregation added to plasma viscosity reduction and non-physiologic flow conditions during extracorporeal circulation are important factors contributing to loss of shear stress at the venous endothelial wall. The loss of shear stress triggers complex signaling leading to endothelial activation. Additional fundamental research is needed in order to verify the hypothesis introduced by the present study. Characterizing the impact of rheologic parameters on endothelial function could prove to be valuable in patients undergoing CPB.
authors.affiliation: Department of Biomedical Engineering, Division of Artificial Organs, University of Medicine Groningen, Faculty of Medical Sciences, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. a.m.morariu@med.rug.nl
authors.forename: Aurora M
authors.initials: AM
authors.lastname: Morariu
authors.forename: Y John
authors.initials: YJ
authors.lastname: Gu
authors.forename: Rolf C G Gallandat
authors.initials: RC
authors.lastname: Huet
authors.forename: Wout A
authors.initials: WA
authors.lastname: Siemons
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rakhorst
authors.forename: Wim V
authors.initials: WV
authors.lastname: Oeveren
mesh_terms: D000328:Adult; D000368:Aged; D001672:Biocompatible Materials; D001809:Blood Viscosity; D002315:Cardiopulmonary Bypass / Q000379:methods*; D002951:Citrates; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D004903:Erythrocyte Aggregation; D006438:Hemodilution / Q000379:methods*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives; D007432:Intraoperative Period; D008875:Middle Aged; D010976:Platelet Count; D016037:Single-Blind Method
chemical_list: D001672:Biocompatible Materials; D002951:Citrates; C485123:HES 130-0.4; D006895:Hydroxyethyl Starch Derivatives; C007999:hydroxycitric acid