title: Veno-venous bypass in liver transplantation: heparin-coated perfusion circuits reduce the activation of humoral defense systems in an in vitro model.
abstract: We studied the effects of bypass circuit surface heparinization on kallikrein-kinin, coagulation, fibrinolytic and complement activation in a closed model system for simulating veno-venous bypass (WBP) in orthotopic liver transplantation (OLT). The circuits were identical to those in routine use during clinical OLT in our institution. Fresh whole human blood diluted 1:2 with Ringer's acetate was circulated at a non-pulsatile flow (2 l/min) and at a constant temperature (37.5 degrees C) for 12 h. In 10 experiments, the entire inner surface of the circuits was coated with end-point attached heparin (HC). In the remaining 10, non-treated PVC tubing was used (NC). Components of the plasma kallikrein-kinin, coagulation, fibrinolytic and complement systems were analyzed using functional techniques (chromogenic peptide substrate assays) and enzyme immunoassays at baseline, 3 and 12 h. Significant activation of the initial (C3bc) and terminal (TCC) components of the complement system were found in both the NC and HC groups after 3 and 12 h: C3bc: NC: baseline = 4 (3.5-7.7), 3 h = 17.3* (12.5-27), 12h = 31* (17.7-63.6), HC: baseline = 4.9 (3.2-6.8), 3h = 9* (6-14.4), 12h = 13.7* (7.4-18.1). TCC: NC: baseline = 0.4 (0.2-0.6), 3h = 5*(0.8-11.9), 12 h: 13.1* (4.2-25.7). HC: baseline = 0.5 (0.1-0.6), 3 h = 0.6* (0.1-0.8), 12 h = 1.2* (0.3-2) AU/ml; median and range (*: p < 0.05). The C3bc and TCC concentrations were significantly higher in the NC group at 3 and 12 h, compared to the HC group: C3bc (NC vs. HC group): 3 h, p < 0.001; 12 h, p < 0.001. TCC (NC vs. HC group): 3h, p < 0.001; 12 h, p < 0.001. Significant increases in the values of thrombin-antithrombin complexes (p = 0.003), prothrombin fragment 1 + 2 (p = 0.006) and plasmin-alpha2-antiplasmin complexes (p = 0.016) were found in the non-coated group, but not in the heparin-coated group during the observation period, showing that the coagulation and fibrinolytic systems were activated in the non-coated circuits. We conclude that heparin-coating of the internal surface of the extracorporeal perfusion circuit used for WBP reduces activation of the plasma cascade systems in a closed venous system in vitro.
authors.affiliation: Institute for Surgical Research and Surgical Department, Rikshospitalet-National Hospital, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Scholz
authors.forename: R
authors.initials: R
authors.lastname: Solberg
authors.forename: C
authors.initials: C
authors.lastname: Okkenhaug
authors.forename: V
authors.initials: V
authors.lastname: Videm
authors.forename: M J
authors.initials: MJ
authors.lastname: Gallimore
authors.forename: O
authors.initials: O
authors.lastname: Mathisen
authors.forename: T
authors.initials: T
authors.lastname: Pedersen
authors.forename: T E
authors.initials: TE
authors.lastname: Mollnes
authors.forename: A
authors.initials: A
authors.lastname: Bergan
authors.forename: O
authors.initials: O
authors.lastname: Søreide
authors.forename: G B
authors.initials: GB
authors.lastname: Klintmalm
authors.forename: A O
authors.initials: AO
authors.lastname: Aasen
mesh_terms: D001779:Blood Coagulation Factors / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology / Q000592:standards; D003167:Complement Activation / Q000187:drug effects; D003176:Complement C3; D003179:Complement C3b; D015938:Complement Membrane Attack Complex / Q000187:drug effects; D005112:Extracorporeal Circulation / Q000295:instrumentation*; D005343:Fibrinolytic Agents / Q000097:blood; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007260:Infusion Pumps; D016234:Kallikrein-Kinin System / Q000187:drug effects; D016031:Liver Transplantation / Q000295:instrumentation*; D010446:Peptide Fragments / Q000097:blood
chemical_list: D001779:Blood Coagulation Factors; C082625:C3 beta c; D020099:Coated Materials, Biocompatible; D003176:Complement C3; D015938:Complement Membrane Attack Complex; D005343:Fibrinolytic Agents; D010446:Peptide Fragments; D003179:Complement C3b; D006493:Heparin