A NEWLY DEVELOPED ANTI-THROMBOCENIC COATING (TNC) AND APPLICATION TO VAD AND AN ECMO SYSTEM

Abstract

We recently developed an innovative anti-thrombogenic coating, called TNC, in which heparin molecules are combined with an aliphatic coupling material for application onto various materials. It has the structure of restraining the leaching of immobilized heparin into blood by enhancing its hydrophobicity with the control of the dialkyl chain length of the coupling agents, which is similar to that of the cell membrane with the lipid layer. We applied TNC to a VAD made of polyurethane, and an ECMO system that consists of our newly developed long-term durable oxygenator constructed of polyolefin and polycarbonate and Jostra Rotaflow centrifugal pump. Three goats underwent a left heart bypass with the VAD and 8 received a veno-arterial bypass with used of the ECMO system. Anticoagulants were not administered to either group. The VADs were continuously driven for 91, 112, and SO days (on going) respectively, according to schedule (bypass flow: 3.0–4.5 L/minute). In the VADs driven for 91 and 112 days perfusions were nearly free from thrombus, while changes in platelet and coagulation related factors, sampled before and 4, 8, and 12 weeks after the initiation of VAD perfusion, were limited within a small range (platelets: 45±11, 37 ± 6, 35±4, and 52 ±5 ×104/mm3, fibrinogen: 247±120, 301±81, 299±136, and 286±1.59 mg/dl, antithrombin 111: 75±1, 101±2, 92±18, and 85±30 %, FDP: 3±4, 3±1, 4±4, and 3±4 μg/mL, XIIIa: 152±23, 200±16, 185±40, and 175±28%, 6-keto PCFl α 17±6, 26±6, 19±3, and 17±0 pg/mL, respectively). The ECMO systems were driven for 21 to 65 (mean 41) days according to schedule (bypass flow: 1.5–3.0 L/minute), and the oxygen and carbon dioxide transfer rates remained constant. Plasma leakage from the oxygenators was completely prevented. Changes of platelet and coagulation related factors, sampled before and 2, 4, and 8 weeks after the initiation of ECMO perfusion, were limited within a small range (platelets: 53±17, 47±18, 39±14, and 43±6×104/mm3, fibrinogen: 292±103, 189±111, 197±55, and 265±57 mg/dl, antithrombin III: 121±14, 136plusmn;9, 132±19, and 122±6%, FDP: 2±2, 3±2, 3±2, and 6±4 μg/mL, XIIIa: 17.5 ±26, 159±15, 164±25, and 143±13%, 6-keto PCFI α:37±18, 31±13, 28± 7, and 23±4 pg/mL respectively). The blood circuits and pumps remained free from thrombus, while in the oxygenators, thrombus formation was rarely observed except for at the margins of the inlet and outlet casings, where the inside blood flow appeared to be most stagnant.