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

Scholz, T.; Solberg, R.; Okkenhaug, C.; Videm, V.; Gallimore, M.J.; Mathisen Ø.; Pedersen, T.; Mollnes, T.E.; Bergan, A.; Søreide, O.; Klintmalm, G.B.; Aasen, A.O.
July 2001
Perfusion;Jul2001, Vol. 16 Issue 4, p285
Academic Journal
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 (VVBP) 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°C) for 12h. 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 12h. 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), 3h = 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: 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): 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-α[sub 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 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 VVBP reduces activation of the plasma cascade systems in a closed venous system in vitro.


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