title: Ex vivo simulation of cardiopulmonary bypass with human blood for hemocompatibility testing.
abstract: Experimental circuits for biomaterial surface testing are frequently limited by the tested blood volume, composition of the circuit, flow conditions and the use of animal blood. This report describes an ex vivo set-up for simulated cardiopulmonary bypass with human blood perfusion. We investigated the clinical generalizability of the observed effects on hematological and metabolic parameters and the hemocompatibility of the system.
  
  
  
  The simulated cardiopulmonary bypass circuit consisted of a heparin-coated tubing system connected to an oxygenator and a venous reservoir. Normothermic flow of blood obtained from healthy donors was maintained at 2.4 L/min/m(2) by a roller pump. Heparin was dosed to obtain a target activated clotting time (ACT) ⩾500 s. Blood was drawn at baseline and 0, 10, 60 and 120 minutes following the initiation of blood flow to determine hematological and metabolic parameters and the hemocompatibility of the extracorporeal system. Data were analyzed using repeated measures ANOVA.
  
  
  
  Two hours of blood perfusion resulted in a small, but clinically unimportant reduction in hematocrit, whereas hemoglobin levels and red blood cell, platelet and leukocyte counts remained stable. There was a significant increase in ACT throughout the experiment. While pO2 levels and the pH remained unaltered during the experiment, pCO2 values decreased from 51 ± 6 mmHg at T0 to 41 ± 3 mmHg at T120 (p<0.001). Simulated cardiopulmonary bypass induced a two-fold increase in C3a (p=0.001) while tissue factor was decreased from 44 ± 14 pg/mL at T0 to 38 ± 13 pg/mL at T120 (p=0.009). Levels of CD40L, prothrombin fragment 1+2, β-thromboglobulin and factor VIIa remained stable over time.
  
  
  
  The ex vivo set-up for simulated cardiopulmonary bypass mimicked the clinical cardiosurgical setting. Exposure of fresh donor blood to the extracorporeal circuit showed a good hemocompatibility, indicated by maintained hematological parameters and a mild immune response.
authors.affiliation: Department of Cardiac and Thoracic Surgery, University Hospital of Angers, Angers, France Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Leylah
authors.initials: L
authors.lastname: Teligui
authors.affiliation: Department of Cardiac and Thoracic Surgery, University Hospital of Angers, Angers, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Dalmayrac
authors.affiliation: Department of Anesthesiology, University Hospital of Angers, Angers, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Corbeau
authors.affiliation: Department of Cardiac and Thoracic Surgery, University Hospital of Angers, Angers, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bouquet
authors.affiliation: Laboratory of Hematology, University Hospital of Angers, Angers, France.
authors.forename: Alban
authors.initials: A
authors.lastname: Godon
authors.affiliation: Laboratory of Immunology, University Hospital of Angers, Angers, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Denommé
authors.affiliation: Department of Cardiac and Thoracic Surgery, University Hospital of Angers, Angers, France.
authors.forename: Partrice
authors.initials: P
authors.lastname: Binuani
authors.affiliation: Department of Cardiac and Thoracic Surgery, University Hospital of Angers, Angers, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Verron
authors.affiliation: Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands c.boer@vumc.nl.
authors.forename: Christa
authors.initials: C
authors.lastname: Boer
authors.affiliation: Department of Cardiac and Thoracic Surgery, University Hospital of Angers, Angers, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Baufreton
mesh_terms: D002315:Cardiopulmonary Bypass; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D008422:Materials Testing / Q000379:methods*; D014914:Whole Blood Coagulation Time
chemical_list: D006493:Heparin
keywords: biosurface; cardiopulmonary bypass; coating; hemostasis; heparin