Veno-venous bypass in liver transplantation: heparin-coated perfusion circuits reduce the activation of humoral defense systems in an in vitro model

We studied the effects of bypass circuit surface heparinization on kallikre in-kinin, coagulation, fibrinolytic and complement activation in a closed m odel system for simulating veno-venous bypass (VVBP) in orthotopic liver tr ansplantation (OLT). The circuits were identical to those in routine use during clinical OFT in our institution. Fresh whole human blood diluted 1:2 with Ringer's acetate was circulated at a non-pulsatile flow 12 l/min) and at a constant temperat ure (37.5 degreesC) for 12 h. in 10 experiments, the entire inner surface o f the circuits was coated with end-point attached heparin [HC). In the rema ining 10, non-treated PVC tubing was used (NC). Components of the plasma ka llikrein-kinin, coagulation, fibrinolytic and complement systems were analy zed 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 an d 12 h: C3bc: NC: baseline = 4 (3.5-7.7). 3 h = 17.3* (12.5-27), 12 h = 31* (17.7-63.6), HC: baseline = 4.9 (3.2-6.8),3 h = 9* (6-14.4), 12 h = 13.7* (7.4-18.1). TCC: NC: baseline = 0.4 (0.2-0.6), 3 h = 5* (0.8-11.9), 12 h: 1 3.1* (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 concent rations were significantly higher in the NC group at 3 and 12 h, compared t o the HC group: C3bc (NC vs. HC group): 3 h, p < 0.001; 12 h, p < 0.001. TC C (NC vs. HC group): 3 h, 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-<alpha>(2)-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 fibri nolytic systems were activated in the non-coated circuits. We conclude that heparin-coating of the internal surface of the extracorpor eal perfusion circuit used for VVBP reduces activation of the plasma cascad e systems in a closed venous system in vitro.