title: Evaluation of a new heparin bonding process in prolonged extracorporeal membrane oxygenation.
abstract: A novel heparin bonding method has been developed for in situ surface modification using ozone oxidation, and evaluated in vitro and in vivo during prolonged extracorporeal membrane oxygenation (ECMO) experiments. The ECMO system consisted of a Capiox hollow fiber membrane oxygenator (MO; Terumo Corp., Tokyo, Japan) with an integral heat exchanger, a Capiox centrifugal pump (CP), and an extracorporeal circuit. The blood contacting surfaces of the system were completely modified using the heparin bonding process, and evaluated in a chronic sheep model for extended period of time, ranging from 96 to 168 hr, under minimal systemic heparinization. The heparin bonded surface was able to maintain high levels of heparin bioactivity, and showed improved blood compatibility in in vitro epifluorescent video microscopy experiments by suppressing platelet adhesion/activation and complement activation. For the ECMO experiments, extracorporeal blood flow was maintained at 3 L/min and the activated clotting time was maintained at 150 sec. There was no significant change in the gas transfer capability or mean pressure drop across the MO over experimental times of up to 168 hr. Platelet count and other coagulation parameters remained stable within the physiologic range throughout the experiment. There were no detectable thrombi in the CP, tubing, or connectors in the test circuit. Local thrombus formation was noted in a stagnant area of the MO, although this did not interfere with its function or lead to any significant embolization. Based on these results, the heparin bonded ECMO system appears to be a safe and effective device for prolonged extracorporeal circulation under minimal systemic heparinization.
authors.affiliation: Institute of Biomedical Science, Terumo Corporation, R&D Center, Kanagawa, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Nojiri
authors.forename: K
authors.initials: K
authors.lastname: Hagiwara
authors.forename: K
authors.initials: K
authors.lastname: Yokoyama
authors.forename: E
authors.initials: E
authors.lastname: Kurbayashi
authors.forename: K
authors.initials: K
authors.lastname: Hidaka
authors.forename: N
authors.initials: N
authors.lastname: Ishida
authors.forename: K
authors.initials: K
authors.lastname: Horiuchi
authors.forename: H
authors.initials: H
authors.lastname: Oshiyama
authors.forename: A
authors.initials: A
authors.lastname: Nogawa
authors.forename: T
authors.initials: T
authors.lastname: Kido
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001672:Biocompatible Materials; D005069:Evaluation Studies as Topic; D015199:Extracorporeal Membrane Oxygenation / Q000295:instrumentation / Q000379:methods*; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D008422:Materials Testing; D008567:Membranes, Artificial; D008855:Microscopy, Electron, Scanning; D012756:Sheep; D013499:Surface Properties; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors
chemical_list: D001672:Biocompatible Materials; D008567:Membranes, Artificial; D000990:Antithrombin III; D006493:Heparin; D013917:Thrombin